{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:44:41Z","timestamp":1760237081000,"version":"build-2065373602"},"reference-count":94,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cytomegalovirus (CMV) is one of the major human health threats worldwide, especially for immunologically comprised patients. CMV may cause opportunistic infections, congenital infections, and brain diseases (e.g., mental retardation and glioblastoma). The etiology of brain diseases associated with human CMV (HCMV) infections is usually complex and it is particularly difficult to treat because HCMV has a life-long infection in its hosts, high mutation rate, and latent infections. Moreover, it is almost impossible to eradicate latent viruses in humans. Although there has been progress in drug discovery recently, current drugs used for treating active CMV infections are still limited in efficacy due to side effects, toxicity, and viral resistance. Fortunately, letermovir which targets the HCMV terminase complex rather than DNA polymerase with fewer adverse reactions has been approved to treat CMV infections in humans. The researchers are focusing on developing approaches against both productive and latent infections of CMV. The gene or RNA targeting approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPR)\/CRISPR-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) are being investigated to remove acute and\/or latent CMV infections. For the treatment of glioblastoma, vaccine therapy through targeting specific CMV antigens has improved patients\u2019 survival outcomes significantly and immunotherapy has also emerged as an alternative modality. The advanced research for developing anti-CMV agents and approaches is promising to obtain significant outcomes and expecting to have a great impact on the therapy of brain diseases associated with CMV infections.<\/jats:p>","DOI":"10.3390\/ijms21041376","type":"journal-article","created":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T04:06:01Z","timestamp":1582085161000},"page":"1376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Potential Therapeutic Approaches Against Brain Diseases Associated with Cytomegalovirus Infections"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7009-5338","authenticated-orcid":false,"given":"Shao-Cheng","family":"Wang","sequence":"first","affiliation":[{"name":"Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan 71742, Taiwan"},{"name":"Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4263-527X","authenticated-orcid":false,"given":"Shiu-Jau","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mackay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Medicine, Mackay Medicine College, New Taipei City 25245, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6592-2845","authenticated-orcid":false,"given":"Yuan-Chuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Program in Comparative Biochemistry, University of California, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"ref_1","first-page":"S45","article-title":"Brain Trauma Foundation: Guidelines for the management of severe traumatic brain injury","volume":"24","author":"Nancy","year":"2007","journal-title":"J. Neurotrauma"},{"key":"ref_2","unstructured":"Johnson, G. (2020, February 17). Traumatic Brain Injury Survival Guide. Available online: www.tbiguide.com."},{"key":"ref_3","unstructured":"(2016, June 10). Mental Disorders. Medline Plus. U.S. National Library of Medicine, Available online: https:\/\/medlineplus.gov\/mentaldisorders.html."},{"key":"ref_4","unstructured":"Derek, B. (2008). What is Mental Disorder? An Essay in Philosophy, Science, and Values, Oxford University Press (OUP). Available online: https:\/\/global.oup.com\/academic\/product\/what-is-mental-disorder-9780198565925."},{"key":"ref_5","unstructured":"(2015, February 07). What Is Neurodegenerative Disease? JPND Research. Available online: http:\/\/www.neurodegenerationresearch.eu\/about\/what\/."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/nature05293","article-title":"Cell death in the nervous system","volume":"443","author":"Bredesen","year":"2006","journal-title":"Nature"},{"key":"ref_7","unstructured":"Lowth, M. (2016, August 11). General Learning Disability. Available online: http:\/\/www.patient.info\/doctor\/general-learning-disability."},{"key":"ref_8","first-page":"1059","article-title":"Identification and evaluation of mental retardation","volume":"61","author":"Daily","year":"2000","journal-title":"Am. Fam. Physician"},{"key":"ref_9","unstructured":"Gale Encyclopedia of Medicine (2020, February 17). Definition of Mentally Retarded. Available online: http:\/\/medical-dictionary.thefreedictionary.com\/mentally%20retarded."},{"key":"ref_10","unstructured":"Kaneshiro, N.K. (2016, October 27). Intellectual disability. MedlinePlus, U.S. National Library of Medicine, Available online: https:\/\/medlineplus.gov\/ency\/article\/001523.htm."},{"key":"ref_11","unstructured":"(2014, June 08). General Information about Adult Brain Tumors. National Cancer Institute (NCI), Available online: http:\/\/www.cancer.gov\/cancertopics\/pdq\/treatment\/adultbrain\/Patient\/page1\/AllPages."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s11060-011-0793-0","article-title":"Recent advances in the molecular understanding of glioblastoma","volume":"108","author":"Bleeker","year":"2012","journal-title":"J. Neuro-Oncol."},{"key":"ref_13","first-page":"121","article-title":"Current trends in the surgical management and treatment of adult glioblastoma","volume":"3","author":"Young","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e273","DOI":"10.3747\/co.22.2436","article-title":"Nonsurgical treatment of recurrent glioblastoma","volume":"22","author":"Gallego","year":"2015","journal-title":"Curr. Oncol."},{"key":"ref_15","unstructured":"(2014, June 08). Adult Brain Tumors Treatment. National Cancer Institute (NCI), Available online: http:\/\/www.cancer.gov\/cancertopics\/pdq\/treatment\/adultbrain\/HealthProfessional\/page1\/AllPages."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s00705-012-1299-6","article-title":"Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses","volume":"157","author":"Adams","year":"2012","journal-title":"Arch. Virol."},{"key":"ref_17","unstructured":"Murray, P.R., Rosenthal, K.S., and Pfaller, M.A. (2005). Medical Microbiology, Elsevier Mosby. [5th ed.]."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7411","DOI":"10.1128\/JVI.74.16.7411-7421.2000","article-title":"Construction and characterization of murine cytomegaloviruses that contain transposon insertions at open reading frames m09 and M83","volume":"74","author":"Zhan","year":"2000","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S1386-6532(02)00096-3","article-title":"Genetic analyses of gene function and pathogenesis of murine cytomegalovirus by transposon-mediated mutagenesis","volume":"25","author":"Lee","year":"2002","journal-title":"J. Clin. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14223","DOI":"10.1073\/pnas.2334032100","article-title":"Functional profiling of a human cytomegalovirus genome","volume":"100","author":"Dunn","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0166-3542(01)00126-7","article-title":"Inhibition of cytomegalovirus immediate early gene expression: A therapeutic option?","volume":"49","author":"Scholz","year":"2001","journal-title":"Antivir. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1128\/AAC.44.6.1588-1597.2000","article-title":"Recombinant green fluorescent protein-expressing human cytomegalovirus as a tool for screening antiviral agents","volume":"44","author":"Marschall","year":"2000","journal-title":"Antimicrob Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.yexmp.2011.10.011","article-title":"Human cytomegalovirus and mucoepidermoid carcinoma of salivary glands: Cell-specific localization of active viral and oncogenic signaling proteins is confirmatory of a causal relationship","volume":"92","author":"Melnick","year":"2012","journal-title":"Exp. Mol. Pathol."},{"key":"ref_24","unstructured":"Gupta, M., and Shorman, M. (2019). Cytomegalovirus, StatPearls Publishing LLC."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1038\/ki.1985.218","article-title":"Reactivation of latent murine cytomegalovirus from kidney","volume":"28","author":"Porter","year":"1985","journal-title":"Kidney Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/rmv.1862","article-title":"Cytomegalovirus latency and reactivation: Recent insights into an old age problem","volume":"26","author":"Dupont","year":"2016","journal-title":"Rev. Med. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"La, Y., Kwon, D.E., Yoo, S.G., Lee, K.H., Han, S.H., and Song, Y.G. (2019). Human cytomegalovirus seroprevalence and titers in solid organ transplant recipients and transplant donors in Seoul, South Korea. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4607-x"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1001\/jama.289.8.1008","article-title":"Maternal immunity and prevention of congenital cytomegalovirus infection","volume":"289","author":"Fowler","year":"2003","journal-title":"JAMA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"297.e1","DOI":"10.1016\/j.ajog.2009.11.018","article-title":"Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus-immune maternal population","volume":"202","author":"Yamamoto","year":"2010","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1086\/508173","article-title":"Seroprevalence of cytomegalovirus infection in the United States, 1988\u20131994","volume":"43","author":"Staras","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"20039","DOI":"10.1073\/pnas.1014509107","article-title":"Experimental human cytomegalovirus latency in CD14+ monocytes","volume":"107","author":"Hargett","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/rmv.544","article-title":"New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection","volume":"17","author":"Dollard","year":"2007","journal-title":"Rev. Med Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/rmv.535","article-title":"Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection","volume":"17","author":"Kenneson","year":"2007","journal-title":"Rev. Med Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1111\/j.1469-0691.2011.03564.x","article-title":"Update on the prevention, diagnosis and management of cytomegalovirus infection during pregnancy","volume":"17","author":"Lazzarotto","year":"2011","journal-title":"Clin. Microbiol. Infect"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/pd.4118","article-title":"A series of 238 cytomegalovirus primary infections during pregnancy: Description and outcome","volume":"33","author":"Picone","year":"2013","journal-title":"Prenat. Diagn."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13052-017-0358-8","article-title":"Congenital cytomegalovirus infection: Advances and challenges in diagnosis, prevention and treatment","volume":"43","author":"Marsico","year":"2017","journal-title":"Ital. J. Pediatr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/00006454-199202000-00007","article-title":"Symptomatic congenital cytomegalovirus infection: Neonatal morbidity and mortality","volume":"11","author":"Boppana","year":"1992","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s00431-006-0172-6","article-title":"Clinical findings and adverse outcome in neonates with symptomatic congenital cytomegalovirus (SCCMV) infection","volume":"165","author":"Kylat","year":"2006","journal-title":"Eur. J. Pediatr."},{"key":"ref_39","first-page":"23","article-title":"Prevention of maternal cytomegalovirus infection: Current status and future prospects","volume":"2","author":"Nyholm","year":"2010","journal-title":"Int. J. Women\u2019s Health"},{"key":"ref_40","first-page":"213","article-title":"Congenital cytomegalovirus infection","volume":"95","author":"Leung","year":"2003","journal-title":"J. Natl. Med. Assoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.jpeds.2013.12.007","article-title":"Spectrum of disease and outcome in children with symptomatic congenital cytomegalovirus infection","volume":"164","author":"Dreher","year":"2014","journal-title":"J. Pediatrics"},{"key":"ref_42","first-page":"335","article-title":"Congenital cytomegalovirus infection: New prospects for prevention and therapy","volume":"60","author":"Swanson","year":"2013","journal-title":"Pediatric Clin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1097\/INF.0b013e31822d9640","article-title":"Congenital cytomegalovirus infection as a cause of sensorineural hearing loss in a highly immune population","volume":"30","author":"Yamamoto","year":"2011","journal-title":"Pediatric Infect. Dis. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jcv.2005.09.016","article-title":"Congenital cytomegalovirus (CMV) infection and hearing deficit","volume":"35","author":"Fowler","year":"2006","journal-title":"J. Clin. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S178","DOI":"10.1093\/cid\/cit629","article-title":"Congenital cytomegalovirus infection: Clinical outcome","volume":"57","author":"Boppana","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1086\/600882","article-title":"Birth prevalence and natural history of congenital cytomegalovirus infection in a highly seroimmune population","volume":"49","author":"Yamamoto","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jcv.2005.09.015","article-title":"Congenital cytomegalovirus infection following first trimester maternal infection: Symptoms at birth and outcome","volume":"35","author":"Pass","year":"2006","journal-title":"J. Clin. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1093\/jac\/dkp083","article-title":"Treatment of congenital cytomegalovirus infection: Implications for future therapeutic strategies","volume":"63","author":"Nassetta","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1097\/01.inf.0000199261.98769.29","article-title":"Multicity Italian study of congenital cytomegalovirus infection","volume":"25","author":"Barbi","year":"2006","journal-title":"Pediatric Infect. Dis. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1515\/JPM.2009.127","article-title":"Guidelines on CMV congenital infection","volume":"37","author":"Coll","year":"2009","journal-title":"J. Perinat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ijid.2019.02.045","article-title":"Cytomegalovirus encephalitis in immunocompetent infants: A 15-year retrospective study at a single center","volume":"82","author":"Guo","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.3389\/fimmu.2019.01776","article-title":"Development of a human cytomegalovirus (HCMV)-based therapeutic cancer vaccine uncovers a previously unsuspected viral block of MHC class I antigen presentation","volume":"10","author":"Abdelaziz","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_53","first-page":"3347","article-title":"Human cytomegalovirus infection and expression in human malignant glioma","volume":"62","author":"Cobbs","year":"2002","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s11908-017-0563-z","article-title":"The viral connection to glioblastoma","volume":"19","author":"Wen","year":"2017","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1172\/JCI123375","article-title":"Cytomegalovirus promotes murine glioblastoma growth via pericyte recruitment and angiogenesis","volume":"130","author":"Krenzlin","year":"2019","journal-title":"J. Clin. Invest."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jcv.2019.04.007","article-title":"New vaccines and antiviral drugs for cytomegalovirus","volume":"116","author":"Griffiths","year":"2019","journal-title":"J. Clin. Virol."},{"key":"ref_57","unstructured":"Medscape (2014, February 04). Vistide (Cidofovir) Dosing, Indications, Interactions, Adverse Effects, and More. Available online: http:\/\/reference.medscape.com\/drug\/vistide-cidofovir-342606#showall."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jmb.2007.03.006","article-title":"Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet","volume":"369","author":"Meyer","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1177\/135965350701200310","article-title":"Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1","volume":"12","author":"Mathiesen","year":"2007","journal-title":"Antivir. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6877","DOI":"10.1523\/JNEUROSCI.0970-17.2017","article-title":"Valnoctamide Inhibits Cytomegalovirus Infection in Developing Brain and Attenuates Neurobehavioral Dysfunctions and Brain Abnormalities","volume":"37","author":"Ornaghi","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/bmb\/ldz031","article-title":"Advances in the treatment of cytomegalovirus","volume":"131","author":"Krishna","year":"2019","journal-title":"Br. Med. Bull."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"ofz375","DOI":"10.1093\/ofid\/ofz375","article-title":"Emergence and persistence of letermovir-resistant cytomegalovirus in a patient with primary immunodeficiency","volume":"6","author":"Popping","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Lin, A., Maloy, M., Su, Y., Bhatt, V., DeRespiris, L., Griffin, M., Lau, C., Proli, A., Barker, J., and Shaffer, B. (2019). Letermovir for primary and secondary cytomegalovirus prevention in allogeneic hematopoietic cell transplant recipients: Real-world experience. Transpl. Infect. Dis., e13187.","DOI":"10.1111\/tid.13187"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Aryal, S., Katugaha, S.B., Cochrane, A., Brown, A.W., Nathan, S.D., Shlobin, O.A., Ahmad, K., Marinak, L., Chun, J., and Fregoso, M. (2019). Single-center experience with use of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients. Transpl. Infect. Dis., e13166.","DOI":"10.1111\/tid.13166"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Veit, T., Munker, D., Kauke, T., Zoller, M., Michel, S., Ceelen, F., Schiopu, S., Barton, J., Arnold, P., and Milger, K. (2019). Letermovir for difficult to treat cytomegalovirus infection in lung transplant recipients. Transplantation.","DOI":"10.1055\/s-0039-3403384"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1056\/NEJMoa1309533","article-title":"Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation","volume":"370","author":"Chemaly","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1056\/NEJMoa1706640","article-title":"Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation","volume":"377","author":"Marty","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMoa1714656","article-title":"Maribavir for preemptive treatment of cytomegalovirus reactivation","volume":"381","author":"Maertens","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1093\/cid\/ciy706","article-title":"Maribavir for refractory or resistant cytomegalovirus infections in hematopoietic-cell or solid-organ transplant recipients: A randomized, dose-ranging, double-blind, phase 2 Study","volume":"68","author":"Papanicolaou","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Hakki, M. (2020). Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy. Curr. Hematol. Malig. Rep.","DOI":"10.1007\/s11899-020-00557-6"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.3390\/v2122740","article-title":"Development of CMX001 for the treatment of poxvirus infections","volume":"2","author":"Lanier","year":"2010","journal-title":"Viruses"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.bbmt.2018.09.038","article-title":"A randomized, double-blind, placebo-controlled phase 3 trial of oral brincidofovir for cytomegalovirus prophylaxis in allogeneic hematopoietic cell transplantation","volume":"25","author":"Marty","year":"2019","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.tibs.2006.04.007","article-title":"RNase P: Interface of the RNA and protein worlds","volume":"31","author":"Evans","year":"2006","journal-title":"Trends Biochem. Sci."},{"key":"ref_75","unstructured":"Gesteland, R., Cech, T., and Atkins, J. (2011). RNase P: Structure and catalysis. The RNA World, Cold Spring Harbor Laboratory Press. Chapter 6.1."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1098\/rstb.2011.0142","article-title":"Ribonuclease P","volume":"366","author":"Altman","year":"2011","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.omtn.2017.10.007","article-title":"Inhibition of murine cytomegalovirus infection in animals by RNase P-associated external guide sequences","volume":"15","author":"Li","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5634","DOI":"10.7150\/thno.27776","article-title":"Engineered RNase P ribozymes effectively inhibit the infection of murine cytomegalovirus in animals","volume":"8","author":"Li","year":"2018","journal-title":"Theranostics"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1261\/rna.069682.118","article-title":"Inhibition of human cytomegalovirus major capsid protein expression and replication by ribonuclease P-associated external guide sequences","volume":"25","author":"Deng","year":"2019","journal-title":"RNA"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Chen, Y.-C., Sheng, J., Trang, P., and Liu, F. (2018). Potential application of the CRISPR\/Cas9 system against herpesvirus infections. Viruses, 10.","DOI":"10.3390\/v10060291"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.virol.2019.01.021","article-title":"Editing the human cytomegalovirus genome with the CRISPR\/Cas9 system","volume":"529","author":"King","year":"2019","journal-title":"Virology"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Van Diemen, F.R., Kruse, E.M., Hooykaas, M.J., Bruggeling, C.E., Sch\u00fcrch, A.C., van Ham, P.M., Imhof, S.M., Nijhuis, M., Wiertz, E.J., and Lebbink, R.J. (2016). CRISPR\/Cas9-mediated genome editing of herpesviruses limits productive and latent Infections. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005701"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Gergen, J., Coulon, F., Creneguy, A., Elain-Duret, N., Gutierrez, A., Pinkenburg, O., Verhoeyen, E., Anegon, I., Nguyen, T.H., and Halary, F.A. (2018). Multiplex CRISPR\/Cas9 system impairs HCMV replication by excising an essential viral gene. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192602"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/nar\/gkq704","article-title":"TAL nucleases (TALNs): Hybrid proteins composed of TAL effectors and FokI DNA-cleavage domain","volume":"39","author":"Li","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1126\/science.1178811","article-title":"Breaking the code of DNA binding specificity of TAL-type III effectors","volume":"326","author":"Boch","year":"2009","journal-title":"Science"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Chen, S.J., and Chen, Y.C. (2019). Potential application of TALENs against murine cytomegalovirus latent infections. Viruses, 11.","DOI":"10.3390\/v11050414"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-1-4939-2432-5_7","article-title":"Synthetic DNA approach to cytomegalovirus vaccine\/immune therapy","volume":"848","author":"Wu","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e29381","DOI":"10.4161\/onci.29381","article-title":"Cellular immunotherapy directed against human cytomegalovirus as a novel approach for glioblastoma treatment","volume":"3","author":"Schuessler","year":"2014","journal-title":"Oncoimmunology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3389\/fonc.2014.00275","article-title":"Cytomegalovirus as a novel target for immunotherapy of glioblastoma multiforme","volume":"4","author":"Schuessler","year":"2014","journal-title":"Front. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"413","DOI":"10.2217\/imt.16.2","article-title":"Cytomegalovirus-targeted immunotherapy and glioblastoma: Hype or hope?","volume":"8","author":"Ferguson","year":"2016","journal-title":"Immunotherapy"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s11060-015-1734-0","article-title":"Cytomegalovirus and glioblastoma; controversies and opportunities","volume":"123","author":"Lawler","year":"2015","journal-title":"J. Neurooncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1158\/1078-0432.CCR-13-3268","article-title":"Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells","volume":"20","author":"Nair","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1158\/1078-0432.CCR-16-2057","article-title":"Long-term survival in glioblastoma with cytomegalovirus pp65-targeted vaccination","volume":"23","author":"Batich","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jocn.2019.03.051","article-title":"Long-term glioblastoma survival following recovery from cytomegalovirus colitis: A case report","volume":"64","author":"Lamano","year":"2019","journal-title":"J. Clin. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/4\/1376\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:58:54Z","timestamp":1760173134000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/4\/1376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,18]]},"references-count":94,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["ijms21041376"],"URL":"https:\/\/doi.org\/10.3390\/ijms21041376","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2020,2,18]]}}}