{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:06:51Z","timestamp":1773277611805,"version":"3.50.1"},"reference-count":167,"publisher":"Bentham Science Publishers Ltd.","issue":"5","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CHR"],"published-print":{"date-parts":[[2019,12,4]]},"abstract":"<jats:sec><jats:title\/><jats:p>Acquired Immunodeficiency Syndrome (AIDS), caused by the Human Immunodeficiency Virus (HIV), is a life-threatening disorder that persists worldwide as a severe health problem. Since it was linked with the HIV attachment process, the Chemokine receptor, CCR5, has been at the development leading edge of several gene-based therapies. Given the shortcomings of the current antiretroviral treatment procedure and the non-availability of a licensed vaccine, the aptitude to modify complex genomes with Designer Nucleases has had a noteworthy impact on biotechnology. Over the last years, ZFN, TALEN and CRISPR\/Cas9 gene-editing technology have appeared as a promising solution that mimics the naturally occurring CCR5\/\u039432 mutation and permanently guarantees the absence of CCR5-expression on the surface of HIV target-cells, leading to a continuous resistance to the virus entry and, ultimately, proving that cellular immunization from infection could be, in fact, a conceivable therapeutic approach to finally achieve the long-awaited functional cure of HIV.<\/jats:p><\/jats:sec>","DOI":"10.2174\/1570162x17666191025112918","type":"journal-article","created":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T13:05:45Z","timestamp":1573736745000},"page":"306-323","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Designer Nucleases: Gene-Editing Therapies using CCR5 as an Emerging Target in HIV"],"prefix":"10.2174","volume":"17","author":[{"given":"Maria Jo\u00e3o","family":"Almeida","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5764-0023","authenticated-orcid":true,"given":"Ana","family":"Matos","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal"}]}],"member":"965","reference":[{"key":"ref=1","author":"Berkhout B","unstructured":"Berkhout B; ERTL HCJ, Weinberg MS. Gene Therapy for HIV and Chronic Infections. American Society of Gene"},{"key":"ref=2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.1998","volume":"28","author":"Deng Q.","year":"2018","unstructured":"Deng Q.; Chen Z.; Shi L.; Lin H.; Developmental progress of CRISPR\/Cas9 and its therapeutic applications for HIV-1 infection. Rev Med Virol 2018,28(5)","journal-title":"Rev Med Virol"},{"key":"ref=3","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/rmv.1739","volume":"23","author":"Nyamweya S.","year":"2013","unstructured":"Nyamweya S.; Hegedus A.; Jaye A.; Rowland-Jones S.; Flanagan K.L.; Macallan D.C.; Comparing HIV-1 and HIV-2 infection: Lessons for viral immunopathogenesis. Rev Med Virol 2013,23(4),221-240","journal-title":"Rev Med Virol"},{"key":"ref=4","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1016\/j.jcyt.2016.07.007","volume":"18","author":"Wang J.","year":"2016","unstructured":"Wang J.; Holmes M.C.; Engineering hematopoietic stem cells toward a functional cure of human immunodeficiency virus infection. Cytotherapy 2016,18(11),1370-1381","journal-title":"Cytotherapy"},{"key":"ref=5","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.1093","volume":"9","author":"Mehta V.","year":"2017","unstructured":"Mehta V.; Chandramohan D.; Agarwal S.; Genetic Modulation Therapy Through Stem Cell Transplantation for Human Immunodeficiency Virus 1 Infection. Cureus 2017,9(3)","journal-title":"Cureus"},{"key":"ref=6","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1080\/14787210.2017.1353911","volume":"15","author":"Huyghe J.","year":"2017","unstructured":"Huyghe J.; Magdalena S.; Vandekerckhove L.; Fight fire with fire: Gene therapy strategies to cure HIV. Expert Rev Anti Infect Ther 2017,15(8),747-758","journal-title":"Expert Rev Anti Infect Ther"},{"key":"ref=7","doi-asserted-by":"publisher","first-page":"2748","DOI":"10.3390\/v5112748","volume":"5","author":"Manjunath N.","year":"2013","unstructured":"Manjunath N.; Yi G.; Dang Y.; Shankar P.; Newer gene editing technologies toward HIV gene therapy. Viruses 2013,5(11),2748-2766","journal-title":"Viruses"},{"key":"ref=8","unstructured":"HIV drug resistance World Health OrganizationAvailable at: https:\/\/www.who.int\/hiv\/topics\/drugresistance\/en\/ [Accessed January 11, 2019]","journal-title":"HIV drug resistance"},{"key":"ref=9","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1101\/cshperspect.a007179","volume":"2","author":"Hoxie J.A.","year":"2012","unstructured":"Hoxie J.A.; June C.H.; Novel cell and gene therapies for HIV. Cold Spring Harb Perspect Med 2012,2(10),2","journal-title":"Cold Spring Harb Perspect Med"},{"key":"ref=10","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.1016\/j.jmb.2018.06.027","volume":"430","author":"Brelot A.","year":"2018","unstructured":"Brelot A.; Chakrabarti L.A.; CCR5 Revisited: How Mechanisms of HIV Entry Govern AIDS Pathogenesis. J Mol Biol 2018,430(17),2557-2589","journal-title":"J Mol Biol"},{"key":"ref=11","unstructured":"Science Daily. Virus. Available at: https:\/\/www.sciencedaily.com\/terms\/virus.htm [Accessed January 13, 2019]."},{"key":"ref=12","unstructured":"AIDS Info. The HIV Life Cycle. [Accessed January 13, 2019]. Available at: https:\/\/aidsinfo.nih.gov\/understanding-hiv-aids\/fact-sheets\/19\/73\/the-hiv-life-cycle"},{"key":"ref=13","doi-asserted-by":"crossref","unstructured":"Kirchhoff F. HIV Life Cycle: Overview. Encyclopedia of AIDS 2013; 1-9.","DOI":"10.1007\/978-1-4614-9610-6_60-1"},{"key":"ref=14","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.atg.2013.05.004","volume":"2","author":"Barmania F.","year":"2013","unstructured":"Barmania F.; Pepper M.S.; C-C chemokine receptor type five (CCR5): An emerging target for the control of HIV infection. Appl Transl Genomics 2013,2,3-16","journal-title":"Appl Transl Genomics"},{"key":"ref=15","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1097\/QAI.0000000000001190","volume":"74","author":"Shi B.","year":"2017","unstructured":"Shi B.; Li J.; Shi X.; TALEN-Mediated Knockout of CCR5 Confers Protection Against Infection of Human Immunodeficiency Virus. J Acquir Immune Defic Syndr 2017,74(2),229-241","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ref=16","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/nrmicro2747","volume":"10","author":"Engelman A.","year":"2012","unstructured":"Engelman A.; Cherepanov P.; The structural biology of HIV-1: mechanistic and therapeutic insights. Nat Rev Microbiol 2012,10(4),279-290","journal-title":"Nat Rev Microbiol"},{"key":"ref=17","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006890","volume":"2","author":"Craigie R.","year":"2012","unstructured":"Craigie R.; Bushman F.D.; HIV DNA integration. Cold Spring Harb Perspect Med 2012,2(7)","journal-title":"Cold Spring Harb Perspect Med"},{"key":"ref=18","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1097\/COH.0b013e3283223d8d","volume":"4","author":"Lodowski D.T.","year":"2009","unstructured":"Lodowski D.T.; Palczewski K.; Chemokine receptors and other G protein-coupled receptors. Curr Opin HIV AIDS 2009,4(2),88-95","journal-title":"Curr Opin HIV AIDS"},{"key":"ref=19","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1002\/iub.1578","volume":"68","author":"Lu M.","year":"2016","unstructured":"Lu M.; Wu B.; Structural studies of G protein-coupled receptors. IUBMB Life 2016,68(11),894-903","journal-title":"IUBMB Life"},{"key":"ref=20","doi-asserted-by":"publisher","first-page":"15495","DOI":"10.1038\/s41598-017-15707-9","volume":"7","author":"Hu G.M.","year":"2017","unstructured":"Hu G.M.; Mai T.L.; Chen C.M.; Visualizing the GPCR Network: Classification and Evolution. Sci Rep 2017,7(1),15495","journal-title":"Sci Rep"},{"key":"ref=21","unstructured":"Guide to Pharmacology. G Protein-Coupled Receptors. Available at: ext-link-type=\"uri\" xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.guidetopharmacology.org\/GRAC\/FamilyDisplay\">http:\/\/www.guidetopharmacology. org\/GRAC\/FamilyDisplay Forward?familyId=694 [Accessed January 19, 2019]."},{"key":"ref=22","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/nature08144","volume":"459","author":"Rosenbaum D.M.","year":"2009","unstructured":"Rosenbaum D.M.; Rasmussen S.G.F.; Kobilka B.K.; The structure and function of G-protein-coupled receptors. Nature 2009,459(7245),356-363","journal-title":"Nature"},{"key":"ref=23","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1146\/annurev.immunol.24.021605.090529","volume":"25","author":"Allen S.J.","year":"2007","unstructured":"Allen S.J.; Crown S.E.; Handel T.M.; Chemokine: receptor structure, interactions, and antagonism. Annu Rev Immunol 2007,25,787-820","journal-title":"Annu Rev Immunol"},{"key":"ref=24","doi-asserted-by":"publisher","first-page":"2944","DOI":"10.1111\/febs.14466","volume":"285","author":"Hughes C.E.","year":"2018","unstructured":"Hughes C.E.; Nibbs R.J.B.; A guide to chemokines and their receptors. FEBS J 2018,285(16),2944-2971","journal-title":"FEBS J"},{"key":"ref=25","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1186\/gb-2006-7-12-243","volume":"7","author":"Zlotnik A.","year":"2006","unstructured":"Zlotnik A.; Yoshie O.; Nomiyama H.; The chemokine and chemokine receptor superfamilies and their molecular evolution. Genome Biol 2006,7(12),243","journal-title":"Genome Biol"},{"key":"ref=26","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.brainresrev.2004.07.021","volume":"48","author":"Cartier L.","year":"2005","unstructured":"Cartier L.; Hartley O.; Dubois-Dauphin M.; Krause K.H.; Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 2005,48(1),16-42","journal-title":"Brain Res Brain Res Rev"},{"key":"ref=27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/gtc.12013","volume":"18","author":"Nomiyama H.","year":"2013","unstructured":"Nomiyama H.; Osada N.; Yoshie O.; Systematic classification of vertebrate chemokines based on conserved synteny and evolutionary history. Genes Cells 2013,18(1),1-16","journal-title":"Genes Cells"},{"key":"ref=28","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.3892\/ijo.2018.4311","volume":"52","author":"Zhang M.","year":"2018","unstructured":"Zhang M.; Zhu Z.L.; Gao X.L.; Wu J.S.; Liang X.H.; Tang Y.L.; Functions of chemokines in the perineural invasion of tumors. (Review). Int J Oncol 2018,52,1019-6439","journal-title":"Int J Oncol"},{"key":"ref=29","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.coviro.2015.06.007","volume":"14","author":"Allers K.","year":"2015","unstructured":"Allers K.; Schneider T.; CCR5\u039432 mutation and HIV infection: basis for curative HIV therapy. Curr Opin Virol 2015,14,24-29","journal-title":"Curr Opin Virol"},{"key":"ref=30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1124\/pr.113.007724","volume":"66","author":"Bachelerie F.","year":"2014","unstructured":"Bachelerie F.; Ben-Baruch A.; Burkhardt A.M.; International Union of Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors. Pharmacol Rev 2014,66,1-79","journal-title":"Pharmacol Rev"},{"key":"ref=31","doi-asserted-by":"publisher","first-page":"9642","DOI":"10.1021\/bi970593z","volume":"36","author":"Pakianathan D.R.","year":"1997","unstructured":"Pakianathan D.R.; Kuta E.G.; Artis D.R.; Skelton N.J.; H\u00e9bert C.A.; Distinct but overlapping epitopes for the interaction of a CC-chemokine with CCR1, CCR3 and CCR5. Biochemistry 1997,36(32),9642-9648","journal-title":"Biochemistry"},{"key":"ref=32","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1182\/blood.V94.6.1899","volume":"94","author":"Blanpain C.","year":"1999","unstructured":"Blanpain C.; Migeotte I.; Lee B.; CCR5 binds multiple CC-chemokines: MCP-3 acts as a natural antagonist. Blood 1999,94(6),1899-1905","journal-title":"Blood"},{"key":"ref=33","doi-asserted-by":"publisher","first-page":"3362","DOI":"10.1021\/bi952950g","volume":"35","author":"Samson M.","year":"1996","unstructured":"Samson M.; Labbe O.; Mollereau C.; Vassart G.; Parmentier M.; Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry 1996,35(11),3362-3367","journal-title":"Biochemistry"},{"key":"ref=34","first-page":"1341","volume":"151","author":"Rottman J.B.","year":"1997","unstructured":"Rottman J.B.; Ganley K.P.; Williams K.; Wu L.; Mackay C.R.; Ringler D.J.; Cellular localization of the chemokine receptor CCR5. Correlation to cellular targets of HIV-1 infection. Am J Pathol 1997,151(5),1341-1351","journal-title":"Am J Pathol"},{"key":"ref=35","doi-asserted-by":"publisher","first-page":"5668","DOI":"10.4049\/jimmunol.178.9.5668","volume":"178","author":"Mummidi S.","year":"2007","unstructured":"Mummidi S.; Adams L.M.; VanCompernolle S.E.; Production of specific mRNA transcripts, usage of an alternate promoter, and octamer-binding transcription factors influence the surface expression levels of the HIV coreceptor CCR5 on primary T cells. J Immunol 2007,178(9),5668-5681","journal-title":"J Immunol"},{"key":"ref=36","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0204989","volume":"13","author":"Hoover K.C.","year":"2018","unstructured":"Hoover K.C.; Intragenus (Homo) Variation in a Chemokine Receptor Gene (CCR5. PLoS One 2018,13(10)","journal-title":"PLoS One"},{"key":"ref=37","doi-asserted-by":"publisher","first-page":"30662","DOI":"10.1074\/jbc.272.49.30662","volume":"272","author":"Mummidi S.","year":"1997","unstructured":"Mummidi S.; Ahuja S.S.; McDaniel B.L.; Ahuja S.K.; The human CC chemokine receptor 5 (CCR5) gene. Multiple transcripts with 5\u2032-end heterogeneity, dual promoter usage, and evidence for polymorphisms within the regulatory regions and noncoding exons. J Biol Chem 1997,272(49),30662-30671","journal-title":"J Biol Chem"},{"key":"ref=38","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.meegid.2010.02.012","volume":"10","author":"Picton A.C.P.","year":"2010","unstructured":"Picton A.C.P.; Paximadis M.; Tiemessen C.T.; Genetic variation within the gene encoding the HIV-1 CCR5 coreceptor in two South African populations. Infect Genet Evol 2010,10(4),487-494","journal-title":"Infect Genet Evol"},{"key":"ref=39","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/S0092-8674(00)80110-5","volume":"86","author":"Liu R.","year":"1996","unstructured":"Liu R.; Paxton W.A.; Choe S.; Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 1996,86(3),367-377","journal-title":"Cell"},{"key":"ref=40","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/4190107","volume":"2017","author":"Heydarifard Z.","year":"2017","unstructured":"Heydarifard Z.; Tabarraei A.; Moradi A.; Polymorphisms in CCR5\u039432 and risk of HIV-1 infection in the Southeast of Caspian Sea, Iran. Dis Markers 2017,2017","journal-title":"Dis Markers"},{"key":"ref=41","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1128\/JVI.78.5.2277-2287.2004","volume":"78","author":"Agrawal L.","year":"2004","unstructured":"Agrawal L.; Lu X.; Qingwen J.; Role for CCR5Delta32 protein in resistance to R5, R5X4, and X4 human immunodeficiency virus type 1 in primary CD4+ cells. J Virol 2004,78(5),2277-2287","journal-title":"J Virol"},{"key":"ref=42","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/382722a0","volume":"382","author":"Samson M.","year":"1996","unstructured":"Samson M.; Libert F.; Doranz B.J.; Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996,382(6593),722-725","journal-title":"Nature"},{"key":"ref=43","author":"Xie Y.","unstructured":"Xie Y.; Zhan S.; Ge W.; Tang P.; The Potential Risks of C-C Chemokine Receptor 5-Edited Babies in Bone Development Bone Research 2019."},{"key":"ref=44","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1126\/science.273.5283.1856","volume":"273","author":"Dean M.","year":"1996","unstructured":"Dean M.; Carrington M.; Winkler C.; Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 1996,273(5283),1856-1862","journal-title":"Science"},{"key":"ref=45","first-page":"219","volume":"19","author":"Smole\u0144-Dzirba J.","year":"2017","unstructured":"Smole\u0144-Dzirba J.; Rosi\u0144ska M.; Janiec J.; HIV-1 infection in persons homozygous for CCR5-\u039432 allele: The next case and the review. AIDS Rev 2017,19(4),219-230","journal-title":"AIDS Rev"},{"key":"ref=46","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1056\/NEJMoa0802905","volume":"360","author":"H\u00fctter G.","year":"2009","unstructured":"H\u00fctter G.; Nowak D.; Mossner M.; Long-term control of HIV by CCR5 Delta32\/Delta32 stem-cell transplantation. N Engl J Med 2009,360(7),692-698","journal-title":"N Engl J Med"},{"key":"ref=47","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s12981-016-0114-y","volume":"13","author":"H\u00fctter G.","year":"2016","unstructured":"H\u00fctter G.; Stem cell transplantation in strategies for curing HIV\/AIDS. AIDS Res Ther 2016,13(1),31","journal-title":"AIDS Res Ther"},{"key":"ref=48","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1172\/JCI80563","volume":"126","author":"Kuritzkes D.R.","year":"2016","unstructured":"Kuritzkes D.R.; Hematopoietic stem cell transplantation for HIV cure. J Clin Invest 2016,126(2),432-437","journal-title":"J Clin Invest"},{"key":"ref=49","doi-asserted-by":"publisher","first-page":"2791","DOI":"10.1182\/blood-2010-09-309591","volume":"117","author":"Allers K.","year":"2011","unstructured":"Allers K.; H\u00fctter G.; Hofmann J.; Evidence for the cure of HIV infection by CCR5\u039432\/\u039432 stem cell transplantation. Blood 2011,117(10),2791-2799","journal-title":"Blood"},{"key":"ref=50","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1097\/QAD.0b013e328340fe28","volume":"25","author":"H\u00fctter G.","year":"2011","unstructured":"H\u00fctter G.; Thiel E.; Allogeneic transplantation of CCR5-deficient progenitor cells in a patient with HIV infection: an update after 3 years and the search for patient no. 2. AIDS 2011,25(2),273-274","journal-title":"AIDS"},{"key":"ref=51","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aae0501","volume":"8","author":"Chhabra A.","year":"2016","unstructured":"Chhabra A.; Ring A.M.; Weiskopf K.; Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy. Sci Transl Med 2016,8","journal-title":"Sci Transl Med"},{"key":"ref=52","unstructured":"Fred Hutch. Timothy Ray Brown: the Accidental AIDS Icon. [Accessed February 14, 2019]. Available at: ext-link-type=\"uri\" xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fredhutch.org\/en\/news\/center-news\/2015\/02\/aids-icon-timothy-ray-brown.html\">http:\/\/www.fredhutch.org\/en\/news\/center-news\/2015\/02\/aids-icon-timothy-ray-brown.html"},{"key":"ref=53","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1517\/14656566.2012.703652","volume":"13","author":"Rezvani A.R.","year":"2012","unstructured":"Rezvani A.R.; Storb R.F.; Prevention of graft-vs.-host disease. Expert Opin Pharmacother 2012,13(12),1737-1750","journal-title":"Expert Opin Pharmacother"},{"key":"ref=54","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3390\/v6010054","volume":"6","author":"Burke B.P.","year":"2013","unstructured":"Burke B.P.; Boyd M.P.; Impey H.; CCR5 as a natural and modulated target for inhibition of HIV. Viruses 2013,6(1),54-68","journal-title":"Viruses"},{"key":"ref=55","author":"Novembre J","unstructured":"Novembre J; Galvani AP; Slatkin M; The geographic spread of the CCR5 delta32 HIV-resistance allele. PLOS biology: A Peer- Reviewed Open-Access Journal 2005; 3: e339."},{"key":"ref=56","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1056\/NEJMc1405805","volume":"371","author":"Kordelas L.","year":"2014","unstructured":"Kordelas L.; Verheyen J.; Beelen D.W.; Shift of HIV tropism in stem-cell transplantation with CCR5 Delta32 mutation. N Engl J Med 2014,371(9),880-882","journal-title":"N Engl J Med"},{"key":"ref=57","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1128\/MMBR.05023-11","volume":"76","author":"Domingo E.","year":"2012","unstructured":"Domingo E.; Sheldon J.; Perales C.; Viral quasispecies evolution. Microbiol Mol Biol Rev 2012,76(2),159-216","journal-title":"Microbiol Mol Biol Rev"},{"key":"ref=58","unstructured":"Complications or side effects of allogeneic stem cell transplant [February 20, 2019]; https:\/\/www.vacancer.com\/diagnosis-and-treatment\/stem-cell-transplantation\/allogeneic-stem-cell-transplant\/complications-or-side-effects-of-allogeneic-stem-cell-transplant\/"},{"key":"ref=59","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1161\/CIRCGENETICS.109.897793","volume":"3","author":"Hyde C.L.","year":"2010","unstructured":"Hyde C.L.; Macinnes A.; Sanders F.A.; Genetic association of the CCR5 region with lipid levels in at-risk cardiovascular patients. Circ Cardiovasc Genet 2010,3(2),162-168","journal-title":"Circ Cardiovasc Genet"},{"key":"ref=60","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1086\/524692","volume":"197","author":"Klein R.S.","year":"2008","unstructured":"Klein R.S.; A moving target: the multiple roles of CCR5 in infectious diseases. J Infect Dis 2008,197(2),183-186","journal-title":"J Infect Dis"},{"key":"ref=61","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1084\/jem.20042530","volume":"202","author":"Glass W.G.","year":"2005","unstructured":"Glass W.G.; Lim J.K.; Cholera R.; Pletnev A.G.; Gao J.L.; Murphy P.M.; Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection. J Exp Med 2005,202(8),1087-1098","journal-title":"J Exp Med"},{"key":"ref=62","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1038\/s41591-019-0459-6","volume":"25","author":"Wei X.","year":"2019","unstructured":"Wei X.; Nielsen R.; CCR5-\u220632 is deleterious in the homozygous state in humans. Nat Med 2019,25(6),909-910","journal-title":"Nat Med"},{"key":"ref=63","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1086\/524709","volume":"197","author":"Kindberg E.","year":"2008","unstructured":"Kindberg E.; Mickien\u00eb A.; Ax C.; A deletion in the chemokine receptor 5 (CCR5) gene is associated with tickborne encephalitis. J Infect Dis 2008,197(2),266-269","journal-title":"J Infect Dis"},{"key":"ref=64","unstructured":"Houses of Parliament. Genome Editing. [Accessed March 12, 2019]. Available at: https:\/\/researchbriefings.files.parliament.uk\/documents\/POST-PN-0541\/POST-PN-0541.pdf"},{"key":"ref=65","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1590\/s1679-45082017rb4024","volume":"15","author":"Gon\u00e7alves G.A.R.","year":"2017","unstructured":"Gon\u00e7alves G.A.R.; Paiva R.M.A.; Gene therapy: advances, challenges and perspectives. Einstein (Sao Paulo) 2017,15(3),369-375","journal-title":"Einstein (Sao Paulo)"},{"key":"ref=66","author":"Rerees H.A.","year":"2018","unstructured":"Rerees H.A.; Es H.A.; Liu D.R.; Base editing: Precision chemistry on the genome and transcriptome of living cells. Nat Rev Genet 2018","journal-title":"Nat Rev Genet"},{"key":"ref=67","unstructured":"amfAR, Making AIDS History. The Countdown to a Cure for AIDS Available at: https:\/\/www.amfar.org\/countdown\/ [Accessed March 15, 2019]."},{"key":"ref=68","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s11904-013-0197-1","volume":"11","author":"Stan R.","year":"2014","unstructured":"Stan R.; Zaia J.A.; Practical considerations in gene therapy for HIV cure. Curr HIV\/AIDS Rep 2014,11(1),11-19","journal-title":"Curr HIV\/AIDS Rep"},{"key":"ref=69","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/nri3262","volume":"12","author":"Deeks S.G.","year":"2012","unstructured":"Deeks S.G.; Autran B.; Berkhout B.; Towards an HIV cure: a global scientific strategy. Nat Rev Immunol 2012,12(8),607-614","journal-title":"Nat Rev Immunol"},{"key":"ref=70","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/ni.3152","volume":"16","author":"Chun T.W.","year":"2015","unstructured":"Chun T.W.; Moir S.; Fauci A.S.; HIV reservoirs as obstacles and opportunities for an HIV cure. Nat Immunol 2015,16(6),584-589","journal-title":"Nat Immunol"},{"key":"ref=71","doi-asserted-by":"publisher","first-page":"264","DOI":"10.2174\/156652308785160674","volume":"8","author":"Nazari R.","year":"2008","unstructured":"Nazari R.; Joshi S.; CCR5 as target for HIV-1 gene therapy. Curr Gene Ther 2008,8(4),264-272","journal-title":"Curr Gene Ther"},{"key":"ref=72","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1097\/COH.0b013e3283223d76","volume":"4","author":"Telenti A.","year":"2009","unstructured":"Telenti A.; Safety concerns about CCR5 as an antiviral target. Curr Opin HIV AIDS 2009,4(2),131-135","journal-title":"Curr Opin HIV AIDS"},{"key":"ref=73","doi-asserted-by":"crossref","first-page":"4018","DOI":"10.4049\/jimmunol.160.8.4018","volume":"160","author":"Zhou Y.","year":"1998","unstructured":"Zhou Y.; Kurihara T.; Ryseck R.P.; Impaired macrophage function and enhanced T cell-dependent immune response in mice lacking CCR5, the mouse homologue of the major HIV-1 coreceptor. J Immunol 1998,160(8),4018-4025","journal-title":"J Immunol"},{"key":"ref=74","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.omtn.2018.11.016","volume":"14","author":"Saha S.K.","year":"2019","unstructured":"Saha S.K.; Saikot F.K.; Rahman M.S.; Programmable molecular scissors: Applications of a new tool for genome editing in biotech. Mol Ther Nucleic Acids 2019,14,212-238","journal-title":"Mol Ther Nucleic Acids"},{"key":"ref=75","unstructured":"The National Academies of Science, Engineering and Medicine. Human Genome Editing: Science, Ethics, and Governance: Somatic Genome Editing. Washington, D.C., EUA: National Academies Press 2017."},{"key":"ref=76","doi-asserted-by":"publisher","first-page":"2546","DOI":"10.1182\/blood-2016-01-678144","volume":"127","author":"Wang C.X.","year":"2016","unstructured":"Wang C.X.; Cannon P.M.; The clinical applications of genome editing in HIV. Blood 2016,127(21),2546-2552","journal-title":"Blood"},{"key":"ref=77","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/mt.2015.54","volume":"23","author":"Corrigan-Curay J.","year":"2015","unstructured":"Corrigan-Curay J.; O\u2019Reilly M.; Kohn D.B.; Genome editing technologies: defining a path to clinic. Mol Ther 2015,23(5),796-806","journal-title":"Mol Ther"},{"key":"ref=78","doi-asserted-by":"publisher","first-page":"D556","DOI":"10.2741\/Singwi","volume":"5","author":"Singwi S.","year":"2000","unstructured":"Singwi S.; Joshi S.; Potential nuclease-based strategies for HIV gene therapy. Front Biosci 2000,5,D556-D579","journal-title":"Front Biosci"},{"key":"ref=79","unstructured":"Thieme. Therapeutic Genome Editing with Engineered Nucleases. [Accessed March 20, 2019]. Available at: https:\/\/www.thieme-connect.com\/products\/ejournals\/abstract\/10.5482\/HAMO-16-09-0035"},{"key":"ref=80","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1038\/nprot.2016.104","volume":"11","author":"Kim J.S.","year":"2016","unstructured":"Kim J.S.; Genome editing comes of age. Nat Protoc 2016,11(9),1573-1578","journal-title":"Nat Protoc"},{"key":"ref=81","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/nbt1398","volume":"26","author":"Meng X.","year":"2008","unstructured":"Meng X.; Noyes M.B.; Zhu L.J.; Lawson N.D.; Wolfe S.A.; Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat Biotechnol 2008,26(6),695-701","journal-title":"Nat Biotechnol"},{"key":"ref=82","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/nature07845","volume":"459","author":"Townsend J.A.","year":"2009","unstructured":"Townsend J.A.; Wright D.A.; Winfrey R.J.; High-frequency modification of plant genes using engineered zinc-finger nucleases. Nature 2009,459(7245),442-445","journal-title":"Nature"},{"key":"ref=83","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1038\/nature03556","volume":"435","author":"Urnov F.D.","year":"2005","unstructured":"Urnov F.D.; Miller J.C.; Lee Y.L.; Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 2005,435(7042),646-651","journal-title":"Nature"},{"key":"ref=84","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/nbt1319","volume":"25","author":"Miller J.C.","year":"2007","unstructured":"Miller J.C.; Holmes M.C.; Wang J.; An improved zinc-finger nuclease architecture for highly specific genome editing. Nat Biotechnol 2007,25(7),778-785","journal-title":"Nat Biotechnol"},{"key":"ref=85","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1126\/science.1178817","volume":"326","author":"Moscou M.J.","year":"2009","unstructured":"Moscou M.J.; Bogdanove A.J.; A simple cipher governs DNA recognition by TAL effectors. Science 2009,326(5959),1501","journal-title":"Science"},{"key":"ref=86","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.tibtech.2013.04.004","volume":"31","author":"Gaj T.","year":"2013","unstructured":"Gaj T.; Gersbach C.A.; Barbas C.F.; ZFN, TALEN, and CRISPR\/Cas-based methods for genome engineering. Trends Biotechnol 2013,31(7),397-405","journal-title":"Trends Biotechnol"},{"key":"ref=87","unstructured":"Leukaemia Foundation. autologous stem cell transplants. Available at: https:\/\/www. leukaemia.org.au\/disease-information\/transplants\/autologous-transplants\/ [Accessed March 25, 2019]."},{"key":"ref=88","unstructured":"Canadian Blood Services. Therapeutic Apheresis. Available at: https:\/\/professionaleducation.blood.ca\/en\/transfusion\/guide-clini que\/therapeutic-apheresis [Accessed March 25, 2019]"},{"key":"ref=89","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/nbt.1663","volume":"28","author":"Holt N.","year":"2010","unstructured":"Holt N.; Wang J.; Kim K.; Human hematopoietic stem\/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat Biotechnol 2010,28(8),839-847","journal-title":"Nat Biotechnol"},{"key":"ref=90","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1038\/mt.2013.65","volume":"21","author":"Li L.","year":"2013","unstructured":"Li L.; Krymskaya L.; Wang J.; Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases. Mol Ther 2013,21(6),1259-1269","journal-title":"Mol Ther"},{"key":"ref=91","unstructured":"Uniprot. Keyword - Zinc-Finger. [Accessed March 22, 2019]. Available at: https:\/\/www.uniprot.org\/keywords\/KW-0863"},{"key":"ref=92","doi-asserted-by":"publisher","first-page":"3061","DOI":"10.1093\/nar\/gkp182","volume":"37","author":"Lippow S.M.","year":"2009","unstructured":"Lippow S.M.; Aha P.M.; Parker M.H.; Blake W.J.; Baynes B.M.; Lipov\u0161ek D.; Creation of a type IIS restriction endonuclease with a long recognition sequence. Nucleic Acids Res 2009,37(9),3061-3073","journal-title":"Nucleic Acids Res"},{"key":"ref=93","doi-asserted-by":"publisher","first-page":"28","DOI":"10.2174\/156652311794520120","volume":"11","author":"H\u00e4ndel E.M.","year":"2011","unstructured":"H\u00e4ndel E.M.; Cathomen T.; Zinc-finger nuclease based genome surgery: it\u2019s all about specificity. Curr Gene Ther 2011,11(1),28-37","journal-title":"Curr Gene Ther"},{"key":"ref=94","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1111\/j.1365-2443.2012.01599.x","volume":"17","author":"Cheng L.T.","year":"2012","unstructured":"Cheng L.T.; Sun L.T.; Tada T.; Genome editing in induced pluripotent stem cells. Genes Cells 2012,17(6),431-438","journal-title":"Genes Cells"},{"key":"ref=95","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1038\/nrg2842","volume":"11","author":"Urnov F.D.","year":"2010","unstructured":"Urnov F.D.; Rebar E.J.; Holmes M.C.; Zhang H.S.; Gregory P.D.; Genome editing with engineered zinc finger nucleases. Nat Rev Genet 2010,11(9),636-646","journal-title":"Nat Rev Genet"},{"key":"ref=96","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.pbi.2010.04.010","volume":"13","author":"Bogdanove A.J.","year":"2010","unstructured":"Bogdanove A.J.; Schornack S.; Lahaye T.; TAL effectors: finding plant genes for disease and defense. Curr Opin Plant Biol 2010,13(4),394-401","journal-title":"Curr Opin Plant Biol"},{"key":"ref=97","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1042\/BJ20140295","volume":"462","author":"Wright D.A.","year":"2014","unstructured":"Wright D.A.; Li T.; Yang B.; Spalding M.H.; TALEN-mediated genome editing: prospects and perspectives. Biochem J 2014,462(1),15-24","journal-title":"Biochem J"},{"key":"ref=98","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.copbio.2012.01.013","volume":"23","author":"Mussolino C.","year":"2012","unstructured":"Mussolino C.; Cathomen T.; TALE nucleases: tailored genome engineering made easy. Curr Opin Biotechnol 2012,23(5),644-650","journal-title":"Curr Opin Biotechnol"},{"key":"ref=99","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr218","volume":"39","author":"Cermak T.","year":"2011","unstructured":"Cermak T.; Doyle E.L.; Christian M.; Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res 2011,39(12)","journal-title":"Nucleic Acids Res"},{"key":"ref=100","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019509","volume":"6","author":"Geissler R.","year":"2011","unstructured":"Geissler R.; Scholze H.; Hahn S.; Transcriptional activators of human genes with programmable DNA-specificity. PLoS One 2011,6(5)","journal-title":"PLoS One"},{"key":"ref=101","unstructured":"Expanding the Genetic Editing Tool Kit: ZFNs, TALENs, and CRISPR-Cas9 [March 24, 2019] https:\/\/www.jci.org\/articles\/view\/72992\/figure\/2"},{"key":"ref=102","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/nmeth.1539","volume":"8","author":"Doyon Y.","year":"2011","unstructured":"Doyon Y.; Vo T.D.; Mendel M.C.; Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures. Nat Methods 2011,8(1),74-79","journal-title":"Nat Methods"},{"key":"ref=103","unstructured":"Beckman Coulter \u2013 Life Sciences. What Is the Difference between Non-Homologous End Joining (NHEJ) and Homology-Directed Repair (HDR)? [Accessed March 24, 2019]. Available at: https:\/\/www.beckman.fr\/support\/faq\/research\/non-homologous-end-joining-(nhej)-and-homology-directed-repair-(hdr)-difference"},{"key":"ref=104","unstructured":"Cambridge Dictionary. Specificity. [Accessed march 22, 2019]. Available at: https:\/\/dictionary.cambridge.org\/dictionary\/english\/specificity"},{"key":"ref=105","doi-asserted-by":"publisher","first-page":"33","DOI":"10.18609\/cgti.2017.005","volume":"3","author":"Chandrasegaran S.","year":"2017","unstructured":"Chandrasegaran S.; Recent advances in the use of ZFN-mediated gene editing for human gene therapy. Cell Gene Ther Insights 2017,3(1),33-41","journal-title":"Cell Gene Ther Insights"},{"key":"ref=106","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1038\/mt.2008.114","volume":"16","author":"Cathomen T.","year":"2008","unstructured":"Cathomen T.; Joung J.K.; Zinc-finger Nucleases: The Next Generation Emerges. Mol Ther 2008,16,1200-1207","journal-title":"Mol Ther"},{"key":"ref=107","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/sj.mt.6300357","volume":"16","author":"Cornu T.I.","year":"2008","unstructured":"Cornu T.I.; Thibodeau-Beganny S.; Guhl E.; Alwin S.; DNA-binding Specificity Is a Major Determinant of the Activity and Toxicity of Zinc-finger Nucleases. Mol Ther 2008,16,352-358","journal-title":"Mol Ther"},{"key":"ref=108","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/nmeth.1680","volume":"8","author":"Mussolino C.","year":"2011","unstructured":"Mussolino C.; Cathomen T.; On target? Tracing zinc-finger-nuclease specificity. Nat Methods 2011,8(9),725-726","journal-title":"Nat Methods"},{"key":"ref=109","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1038\/nmeth.1670","volume":"8","author":"Pattanayak V.","year":"2011","unstructured":"Pattanayak V.; Ramirez C.L.; Joung J.K.; Liu D.R.; Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection. Nat Methods 2011,8(9),765-770","journal-title":"Nat Methods"},{"key":"ref=110","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/nmeth.2845","volume":"11","author":"Guilinger J.P.","year":"2014","unstructured":"Guilinger J.P.; Pattanayak V.; Reyon D.; Broad specificity profiling of TALENs results in engineered nucleases with improved DNA-cleavage specificity. Nat Methods 2014,11(4),429-435","journal-title":"Nat Methods"},{"key":"ref=111","doi-asserted-by":"publisher","first-page":"6762","DOI":"10.1093\/nar\/gku305","volume":"42","author":"Mussolino C.","year":"2014","unstructured":"Mussolino C.; Alzubi J.; Fine E.J.; TALENs facilitate targeted genome editing in human cells with high specificity and low cytotoxicity. Nucleic Acids Res 2014,42(10),6762-6773","journal-title":"Nucleic Acids Res"},{"key":"ref=112","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1363","volume":"42","author":"Lin Y.","year":"2014","unstructured":"Lin Y.; Fine E.J.; Zheng Z.; SAPTA: a new design tool for improving TALE nuclease activity. Nucleic Acids Res 2014,42(6)","journal-title":"Nucleic Acids Res"},{"key":"ref=113","doi-asserted-by":"publisher","first-page":"8150","DOI":"10.1038\/srep08150","volume":"5","author":"Juillerat A.","year":"2015","unstructured":"Juillerat A.; Pessereau C.; Dubois G.; Optimized tuning of TALEN specificity using non-conventional RVDs. Sci Rep 2015,5,8150","journal-title":"Sci Rep"},{"key":"ref=114","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1093\/nar\/27.2.674","volume":"27","author":"Smith J.","year":"1999","unstructured":"Smith J.; Berg J.M.; Chandrasegaran S.; A detailed study of the substrate specificity of a chimeric restriction enzyme. Nucleic Acids Res 1999,27(2),674-681","journal-title":"Nucleic Acids Res"},{"key":"ref=115","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1038\/nbt1317","volume":"25","author":"Szczepek M.","year":"2007","unstructured":"Szczepek M.; Brondani V.; B\u00fcchel J.; Serrano L.; Segal D.J.; Cathomen T.; Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases. Nat Biotechnol 2007,25(7),786-793","journal-title":"Nat Biotechnol"},{"key":"ref=116","doi-asserted-by":"publisher","first-page":"10564","DOI":"10.1073\/pnas.95.18.10564","volume":"95","author":"Wah D.A.","year":"1998","unstructured":"Wah D.A.; Bitinaite J.; Schildkraut I.; Aggarwal A.K.; Structure of FokI has implications for DNA cleavage. Proc Natl Acad Sci USA 1998,95(18),10564-10569","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref=117","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/mt.2008.233","volume":"17","author":"H\u00e4ndel E.M.","year":"2009","unstructured":"H\u00e4ndel E.M.; Alwin S.; Cathomen T.; Expanding or restricting the target site repertoire of zinc-finger nucleases: the inter-domain linker as a major determinant of target site selectivity. Mol Ther 2009,17(1),104-111","journal-title":"Mol Ther"},{"key":"ref=118","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1038\/aps.2017.2","volume":"38","author":"Shim G.","year":"2017","unstructured":"Shim G.; Kim D.; Park G.T.; Jin H.; Suh S.K.; Oh Y.K.; Therapeutic gene editing: delivery and regulatory perspectives. Acta Pharmacol Sin 2017,38(6),738-753","journal-title":"Acta Pharmacol Sin"},{"key":"ref=119","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/BF03256872","volume":"25","author":"Kamimura K.","year":"2011","unstructured":"Kamimura K.; Suda T.; Zhang G.; Liu D.; Advances in Gene Delivery Systems. Pharmaceut Med 2011,25(5),293-306","journal-title":"Pharmaceut Med"},{"key":"ref=120","doi-asserted-by":"publisher","first-page":"30675","DOI":"10.18632\/oncotarget.5169","volume":"6","author":"Chira S.","year":"2015","unstructured":"Chira S.; Jackson C.S.; Oprea I.; Progresses towards safe and efficient gene therapy vectors. Oncotarget 2015,6(31),30675-30703","journal-title":"Oncotarget"},{"key":"ref=121","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nm.3793","volume":"21","author":"Cox D.B.T.","year":"2015","unstructured":"Cox D.B.T.; Platt R.J.; Zhang F.; Therapeutic genome editing: prospects and challenges. Nat Med 2015,21(2),121-131","journal-title":"Nat Med"},{"key":"ref=122","doi-asserted-by":"publisher","first-page":"4","DOI":"10.4172\/2157-7412.1000237","volume":"5","author":"Loske A.M.","year":"2014","unstructured":"Loske A.M.; Fern\u00e1ndez F.; G\u00f3mez-Lim M.; Rivera A.L.; Genetic Transformation of Cells using Physical Methods. J Genet Syndr Gene Ther 2014,5,4","journal-title":"J Genet Syndr Gene Ther"},{"key":"ref=123","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4103\/2277-9175.98152","volume":"1","author":"Nayerossadat N.","year":"2012","unstructured":"Nayerossadat N.; Maedeh T.; Ali P.A.; Viral and nonviral delivery systems for gene delivery. Adv Biomed Res 2012,1,27","journal-title":"Adv Biomed Res"},{"key":"ref=124","doi-asserted-by":"publisher","first-page":"2721","DOI":"10.3390\/ijms19092721","volume":"19","author":"Ho B.X.","year":"2018","unstructured":"Ho B.X.; Loh S.J.H.; Chan W.K.; Soh B.S.; In vivo genome editing as a therapeutic approach. Int J Mol Sci 2018,19(9),2721","journal-title":"Int J Mol Sci"},{"key":"ref=125","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nrg3742","volume":"15","author":"Kotterman M.A.","year":"2014","unstructured":"Kotterman M.A.; Schaffer D.V.; Engineering adeno-associated viruses for clinical gene therapy. Nat Rev Genet 2014,15(7),445-451","journal-title":"Nat Rev Genet"},{"key":"ref=126","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1128\/CMR.00008-08","volume":"21","author":"Daya S.","year":"2008","unstructured":"Daya S.; Berns K.I.; Gene therapy using adeno-associated virus vectors. Clin Microbiol Rev 2008,21(4),583-593","journal-title":"Clin Microbiol Rev"},{"key":"ref=127","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.csbj.2016.12.006","volume":"15","author":"Guha T.K.","year":"2017","unstructured":"Guha T.K.; Wai A.; Hausner G.; Programmable genome editing tools and their regulation for efficient genome engineering. Comput Struct Biotechnol J 2017,15,146-160","journal-title":"Comput Struct Biotechnol J"},{"key":"ref=128","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1126\/science.1225829","volume":"337","author":"Jinek M.","year":"2012","unstructured":"Jinek M.; Chylinski K.; Fonfara I.; Hauer M.; Doudna J.A.; Charpentier E.; A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012,337(6096),816-821","journal-title":"Science"},{"key":"ref=129","author":"Lin C.","year":"2014","unstructured":"Lin C.; Characterization and Optimization of the CRISPR\/Cas System for Applications in Genome Engineering 2014","journal-title":"Characterization and Optimization of the CRISPR\/Cas System for Applications in Genome Engineering"},{"key":"ref=130","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nrmicro1793","volume":"6","author":"Sorek R.","year":"2008","unstructured":"Sorek R.; Kunin V.; Hugenholtz P.; CRISPR--a widespread system that provides acquired resistance against phages in bacteria and archaea. Nat Rev Microbiol 2008,6(3),181-186","journal-title":"Nat Rev Microbiol"},{"key":"ref=131","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.1099\/mic.0.28048-0","volume":"151","author":"Bolotin A.","year":"2005","unstructured":"Bolotin A.; Quinquis B.; Sorokin A.; Ehrlich S.D.; Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology 2005,151(Pt 8),2551-2561","journal-title":"Microbiology"},{"key":"ref=132","unstructured":"Bacteriophage. https:\/\/www.britannica.com\/science\/bacteriophage [March 28, 2019]"},{"key":"ref=133","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1126\/science.1138140","volume":"315","author":"Barrangou R.","year":"2007","unstructured":"Barrangou R.; Fremaux C.; Deveau H.; CRISPR provides acquired resistance against viruses in prokaryotes. Science 2007,315(5819),1709-1712","journal-title":"Science"},{"key":"ref=134","unstructured":"There\u2019s CRISPR in Your Yogurt. https:\/\/www.the-scientist.com\/notebook\/theres-crispr-in-your-yogurt-36142 [March 29, 2019]."},{"key":"ref=135","doi-asserted-by":"publisher","first-page":"257","DOI":"10.3389\/fmicb.2018.00257","volume":"9","author":"Hao M.","year":"2018","unstructured":"Hao M.; Cui Y.; Qu X.; Analysis of CRISPR-cas system in Streptococcus thermophilus and its application. Front Microbiol 2018,9,257","journal-title":"Front Microbiol"},{"key":"ref=136","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1038\/ncomms1937","volume":"3","author":"Datsenko K.A.","year":"2012","unstructured":"Datsenko K.A.; Pougach K.; Tikhonov A.; Wanner B.L.; Severinov K.; Semenova E.; Molecular memory of prior infections activates the CRISPR\/Cas adaptive bacterial immunity system. Nat Commun 2012,3,945","journal-title":"Nat Commun"},{"key":"ref=137","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1046\/j.1365-2958.2002.02839.x","volume":"43","author":"Jansen R.","year":"2002","unstructured":"Jansen R.; Embden J.D.; Gaastra W.; Schouls L.M.; Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol 2002,43(6),1565-1575","journal-title":"Mol Microbiol"},{"key":"ref=138","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1126\/science.1232033","volume":"339","author":"Mali P.","year":"2013","unstructured":"Mali P.; Yang L.; Esvelt K.M.; RNA-guided human genome engineering via Cas9. Science 2013,339(6121),823-826","journal-title":"Science"},{"key":"ref=139","doi-asserted-by":"publisher","first-page":"R40","DOI":"10.1093\/hmg\/ddu125","volume":"23","author":"Zhang F.","year":"2014","unstructured":"Zhang F.; Wen Y.; Guo X.; CRISPR\/Cas9 for genome editing: progress, implications and challenges. Hum Mol Genet 2014,23(R1),R40-R46","journal-title":"Hum Mol Genet"},{"key":"ref=140","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3389\/fcimb.2019.00069","volume":"9","author":"Xiao Q.","year":"2019","unstructured":"Xiao Q.; Guo D.; Chen S.; Application of CRISPR\/Cas9-Based Gene Editing in HIV-1\/AIDS Therapy. Front Cell Infect Microbiol 2019,9,69","journal-title":"Front Cell Infect Microbiol"},{"key":"ref=141","doi-asserted-by":"publisher","first-page":"2940","DOI":"10.3389\/fmicb.2018.02940","volume":"9","author":"Allen A.G.","year":"2018","unstructured":"Allen A.G.; Chung C.H.; Atkins A.; Gene Editing of HIV-1 Co-receptors to Prevent and\/or Cure Virus Infection. Front Microbiol 2018,9,2940","journal-title":"Front Microbiol"},{"key":"ref=142","doi-asserted-by":"publisher","first-page":"6091","DOI":"10.1093\/nar\/gku241","volume":"42","author":"Chylinski K.","year":"2014","unstructured":"Chylinski K.; Makarova K.S.; Charpentier E.; Koonin E.V.; Classification and evolution of type II CRISPR-Cas systems. Nucleic Acids Res 2014,42(10),6091-6105","journal-title":"Nucleic Acids Res"},{"key":"ref=143","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.1231143","volume":"339","author":"Cong L.","year":"2013","unstructured":"Cong L.; Ran F.A.; Cox D.; Multiplex genome engineering using CRISPR\/Cas systems. Science 2013,339(6121),819-823","journal-title":"Science"},{"key":"ref=144","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1080\/15476286.2019.1582974","volume":"16","author":"Le Rhun A.","year":"2019","unstructured":"Le Rhun A.; Escalera-Maurer A.; Bratovi\u010d M.; Charpentier E.; CRISPR-Cas in Streptococcus pyogenes. RNA Biol 2019,16(4),380-389","journal-title":"RNA Biol"},{"key":"ref=145","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.bcmd.2016.09.003","volume":"62","author":"Hu X.","year":"2016","unstructured":"Hu X.; CRISPR\/Cas9 system and its applications in human hematopoietic cells. Blood Cells Mol Dis 2016,62,6-12","journal-title":"Blood Cells Mol Dis"},{"key":"ref=146","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035888","volume":"7","author":"Swarts D.C.","year":"2012","unstructured":"Swarts D.C.; Mosterd C.; van Passel M.W.J.; Brouns S.J.J.; CRISPR interference directs strand specific spacer acquisition. PLoS One 2012,7(4)","journal-title":"PLoS One"},{"key":"ref=147","doi-asserted-by":"publisher","author":"Dai WJ","unstructured":"Dai WJ; Zhu LY; Yan ZY; Xu Y; Wang QL; Lu XJ; CRISPR-Cas9 for in vivo Gene Therapy: Promise and Hurdles. Mol Ther Nucleic Acids 2016; 5e349.","DOI":"10.1038\/mtna.2016.58"},{"key":"ref=148","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1080\/10717544.2018.1474964","volume":"25","author":"Lino C.A.","year":"2018","unstructured":"Lino C.A.; Harper J.C.; Carney J.P.; Timlin J.A.; Delivering CRISPR: a review of the challenges and approaches. Drug Deliv 2018,25(1),1234-1257","journal-title":"Drug Deliv"},{"key":"ref=149","author":"Lin C.","unstructured":"Lin C.; Characterization and Optimization of the CRISPR\/Cas System for Applications in Genome Engineering Doctoral dissertation, Office of Scholarly Communication at Harvard Medical School 2014."},{"key":"ref=150","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/s40484-014-0030-x","volume":"2","author":"Wu X.","year":"2014","unstructured":"Wu X.; Kriz A.J.; Sharp P.A.; Target specificity of the CRISPR-Cas9 system. Quant Biol 2014,2(2),59-70","journal-title":"Quant Biol"},{"key":"ref=151","doi-asserted-by":"publisher","first-page":"5186","DOI":"10.1111\/febs.13110","volume":"281","author":"Ma Y.","year":"2014","unstructured":"Ma Y.; Zhang L.; Huang X.; Genome modification by CRISPR\/Cas9. FEBS J 2014,281(23),5186-5193","journal-title":"FEBS J"},{"key":"ref=152","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1517\/14712598.2015.1036736","volume":"15","author":"Saayman S.","year":"2015","unstructured":"Saayman S.; Ali S.A.; Morris K.V.; Weinberg M.S.; The therapeutic application of CRISPR\/Cas9 technologies for HIV. Expert Opin Biol Ther 2015,15(6),819-830","journal-title":"Expert Opin Biol Ther"},{"key":"ref=153","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jconrel.2017.09.012","volume":"266","author":"Liu C.","year":"2017","unstructured":"Liu C.; Zhang L.; Liu H.; Cheng K.; Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications. J Control Release 2017,266,17-26","journal-title":"J Control Release"},{"key":"ref=154","doi-asserted-by":"publisher","author":"Oude Blenke E","unstructured":"Oude Blenke E; Evers MJW; Mastrobattista E; van der Oost J; CRISPR-Cas9 gene editing: Delivery aspects and therapeutic potential. J Control Release 2016; 244(Pt B): 139-48","DOI":"10.1016\/j.jconrel.2016.08.002"},{"key":"ref=155","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3791\/56275","author":"Elaswad A.","year":"2018","unstructured":"Elaswad A.; Khalil K.; Cline D.; Microinjection of CRISPR\/Cas9 Protein into Channel Catfish, Ictalurus punctatus, Embryos for Gene Editing. J Vis Exp 2018,131","journal-title":"J Vis Exp"},{"key":"ref=156","unstructured":"Fact Sheets about Microinjection \u2014 the Definition, Types, Advantages and Applications [April 7, 2019]; https:\/\/medium.com\/@contact_28660\/fact-sheets-about-microinjection-the-definitio"},{"key":"ref=157","author":"Potter H.","unstructured":"Potter H.; Transfection by electroporation. Curr Protoc Mol Biol 2003; Chapter 9: 3."},{"key":"ref=158","author":"Xu L.","unstructured":"Xu L.; Wang J.; Liu Y.; CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia. N Engl J Med 2019; 381: 1240-1247."},{"key":"ref=159","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/mt.2009.255","volume":"18","author":"Wu Z.","year":"2010","unstructured":"Wu Z.; Yang H.; Colosi P.; Effect of genome size on AAV vector packaging. Mol Ther 2010,18(1),80-86","journal-title":"Mol Ther"},{"key":"ref=160","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/nature14299","volume":"520","author":"Ran F.A.","year":"2015","unstructured":"Ran F.A.; Cong L.; Yan W.X.; In vivo genome editing using Staphylococcus aureus Cas9. Nature 2015,520(7546),186-191","journal-title":"Nature"},{"key":"ref=161","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3390\/v11010028","volume":"11","author":"Xu C.L.","year":"2019","unstructured":"Xu C.L.; Ruan M.Z.C.; Mahajan V.B.; Tsang S.H.; Viral Delivery Systems for CRISPR. Viruses 2019,11(1),28","journal-title":"Viruses"},{"key":"ref=162","doi-asserted-by":"publisher","first-page":"5405","DOI":"10.1038\/srep05405","volume":"4","author":"Zhang Y.","year":"2014","unstructured":"Zhang Y.; Ge X.; Yang F.; Comparison of non-canonical PAMs for CRISPR\/Cas9-mediated DNA cleavage in human cells. Sci Rep 2014,4,5405","journal-title":"Sci Rep"},{"key":"ref=163","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2015.37","volume":"4","author":"Zhang X.H.","year":"2015","unstructured":"Zhang X.H.; Tee L.Y.; Wang X.G.; Huang Q.S.; Yang S.H.; Off-target Effects in CRISPR\/Cas9-mediated Genome Engineering. Mol Ther Nucleic Acids 2015,4","journal-title":"Mol Ther Nucleic Acids"},{"key":"ref=164","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1093\/nar\/gkx1268","volume":"46","author":"Labuhn M.","year":"2018","unstructured":"Labuhn M.; Adams F.F.; Ng M.; Refined sgRNA efficacy prediction improves large- and small-scale CRISPR-Cas9 applications. Nucleic Acids Res 2018,46(3),1375-1385","journal-title":"Nucleic Acids Res"},{"key":"ref=165","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nbt.2909","volume":"32","author":"Guilinger J.P.","year":"2014","unstructured":"Guilinger J.P.; Thompson D.B.; Liu D.R.; Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat Biotechnol 2014,32(6),577-582","journal-title":"Nat Biotechnol"},{"key":"ref=166","doi-asserted-by":"publisher","first-page":"2753","DOI":"10.1038\/s41467-019-10366-y","volume":"10","author":"Dash P.K.","year":"2019","unstructured":"Dash P.K.; Kaminski R.; Bella R.; Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice. Nat Commun 2019,10(1),2753","journal-title":"Nat Commun"},{"key":"ref=167","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1111\/pbi.12448","volume":"14","author":"Weeks D.P.","year":"2016","unstructured":"Weeks D.P.; Spalding M.H.; Yang B.; Use of designer nucleases for targeted gene and genome editing in plants. Plant Biotechnol J 2016,14(2),483-495","journal-title":"Plant Biotechnol J"}],"container-title":["Current HIV Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/eurekaselect.com\/article\/download\/176171","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T22:59:59Z","timestamp":1695423599000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.eurekaselect.com\/176171\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,4]]},"references-count":167,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,12,4]]}},"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/1570162x17666191025112918","relation":{},"ISSN":["1570-162X"],"issn-type":[{"value":"1570-162X","type":"print"}],"subject":[],"published":{"date-parts":[[2019,12,4]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2019-09-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-16","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}