{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:04:44Z","timestamp":1791813884037,"version":"4.3.4"},"reference-count":150,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of the People\u2019s Republic of China, National Key Research and Development Program of China","award":["2021YFF1200800"],"award-info":[{"award-number":["2021YFF1200800"]}]},{"name":"Ministry of Science and Technology of the People\u2019s Republic of China, National Key Research and Development Program of China","award":["2022YFF1202903"],"award-info":[{"award-number":["2022YFF1202903"]}]},{"name":"Ministry of Science and Technology of the People\u2019s Republic of China, National Key Research and Development Program of China","award":["82101853"],"award-info":[{"award-number":["82101853"]}]},{"name":"National Natural Science Foundation of China, the Youth Fund of the National Natural Science Foundation of China","award":["2021YFF1200800"],"award-info":[{"award-number":["2021YFF1200800"]}]},{"name":"National Natural Science Foundation of China, the Youth Fund of the National Natural Science Foundation of China","award":["2022YFF1202903"],"award-info":[{"award-number":["2022YFF1202903"]}]},{"name":"National Natural Science Foundation of China, the Youth Fund of the National Natural Science Foundation of China","award":["82101853"],"award-info":[{"award-number":["82101853"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Viral vectors play a pivotal role in the field of gene therapy, with several related drugs having already gained clinical approval from the EMA and FDA. However, numerous viral gene therapy vectors are currently undergoing pre-clinical research or participating in clinical trials. Despite advancements, the innate response remains a significant barrier impeding the clinical development of viral gene therapy. The innate immune response to viral gene therapy vectors and transgenes is still an important reason hindering its clinical development. Extensive studies have demonstrated that different DNA and RNA sensors can detect adenoviruses, adeno-associated viruses, and lentiviruses, thereby activating various innate immune pathways such as Toll-like receptor (TLR), cyclic GMP-AMP synthase\u2013stimulator of interferon genes (cGAS-STING), and retinoic acid-inducible gene I\u2013mitochondrial antiviral signaling protein (RLR-MAVS). This review focuses on elucidating the mechanisms underlying the innate immune response induced by three widely utilized viral vectors: adenovirus, adeno-associated virus, and lentivirus, as well as the strategies employed to circumvent innate immunity.<\/jats:p>","DOI":"10.3390\/v15091801","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T10:09:53Z","timestamp":1692871793000},"page":"1801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Innate Immune Response to Viral Vectors in Gene Therapy"],"prefix":"10.3390","volume":"15","author":[{"given":"Yixuan","family":"Wang","sequence":"first","affiliation":[{"name":"Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwei","family":"Shao","sequence":"additional","affiliation":[{"name":"Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sato-Dahlman, M., LaRocca, C.J., Yanagiba, C., and Yamamoto, M. (2020). Adenovirus and Immunotherapy: Advancing Cancer Treatment by Combination. Cancers, 12.","DOI":"10.3390\/cancers12051295"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-associated virus vector as a platform for gene therapy delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.ymthe.2020.01.001","article-title":"Immune Responses to Viral Gene Therapy Vectors","volume":"28","author":"Shirley","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/sj.mt.6300024","article-title":"Type I interferon inhibits antibody responses induced by a chimpanzee adenovirus vector","volume":"15","author":"Hensley","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_5","first-page":"493","article-title":"Evading the immune response upon in vivo gene therapy with viral vectors","volume":"11","author":"Sack","year":"2009","journal-title":"Curr. Opin. Mol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3389\/fmicb.2011.00194","article-title":"Innate Immune Responses to AAV Vectors","volume":"2","author":"Rogers","year":"2011","journal-title":"Front. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.coviro.2011.05.013","article-title":"Innate immunity modulation in virus entry","volume":"1","author":"Faure","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/s41577-021-00524-z","article-title":"The cGAS-STING pathway as a therapeutic target in inflammatory diseases","volume":"21","author":"Decout","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Atasheva, S., and Shayakhmetov, D.M. (2022). Cytokine Responses to Adenovirus and Adenovirus Vectors. Viruses, 14.","DOI":"10.3390\/v14050888"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.1002\/1873-3468.13680","article-title":"Adenoviral strategies to overcome innate cellular responses to infection","volume":"593","author":"Sohn","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.virusres.2015.06.018","article-title":"Adenovirus VA RNA: An essential pro-viral non-coding RNA","volume":"212","author":"Vachon","year":"2016","journal-title":"Virus Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rabinowitz, J., Chan, Y.K., and Samulski, R.J. (2019). Adeno-associated Virus (AAV) versus Immune Response. Viruses, 11.","DOI":"10.3390\/v11020102"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e143780","DOI":"10.1172\/JCI143780","article-title":"Overcoming innate immune barriers that impede AAV gene therapy vectors","volume":"131","author":"Muhuri","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bergantz, L., Subra, F., Deprez, E., Delelis, O., and Richetta, C. (2019). Interplay between Intrinsic and Innate Immunity during HIV Infection. Cells, 8.","DOI":"10.3390\/cells8080922"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1089\/hum.2005.16.1014","article-title":"Gendicine: The first commercial gene therapy product","volume":"16","author":"Wilson","year":"2005","journal-title":"Hum. Gene Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2174\/1568009618666171129221503","article-title":"Oncorine, the World First Oncolytic Virus Medicine and its Update in China","volume":"18","author":"Liang","year":"2018","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1038\/mt.2012.194","article-title":"Endgame: Glybera finally recommended for approval as the first gene therapy drug in the European union","volume":"20","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11095-018-2554-7","article-title":"Pharmaceutical Development of AAV-Based Gene Therapy Products for the Eye","volume":"36","author":"Rodrigues","year":"2018","journal-title":"Pharm. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e321","DOI":"10.1634\/theoncologist.2019-0233","article-title":"The European Medicines Agency Review of Kymriah (Tisagenlecleucel) for the Treatment of Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma","volume":"25","author":"Ali","year":"2020","journal-title":"Oncologist"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1007\/s40264-021-01107-6","article-title":"Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy","volume":"44","author":"Day","year":"2021","journal-title":"Drug Saf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"695937","DOI":"10.3389\/fnmol.2021.695937","article-title":"Current and Future Prospects for Gene Therapy for Rare Genetic Diseases Affecting the Brain and Spinal Cord","volume":"14","author":"Jensen","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s40291-021-00555-1","article-title":"Elivaldogene Autotemcel: First Approval","volume":"25","author":"Keam","year":"2021","journal-title":"Mol. Diagn. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"876339","DOI":"10.3389\/fimmu.2022.876339","article-title":"Impact of Manufacturing Procedures on CAR T Cell Functionality","volume":"13","author":"Watanabe","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_24","first-page":"1427","article-title":"Eladocagene Exuparvovec: First Approval","volume":"82","author":"Keam","year":"2022","journal-title":"Drugs"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1007\/s40265-022-01788-y","article-title":"Valoctocogene Roxaparvovec: First Approval","volume":"82","author":"Blair","year":"2022","journal-title":"Drugs"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s40265-023-01902-8","article-title":"Correction to: Nadofaragene Firadenovec: First Approval","volume":"83","author":"Lee","year":"2023","journal-title":"Drugs"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/cpt.1639","article-title":"Regulators\u2019 Advice Can Make a Difference: European Medicines Agency Approval of Zynteglo for Beta Thalassemia","volume":"107","author":"Enzmann","year":"2020","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Nishikawaji, Y., Kawakami, H., and Kosai, K.I. (2021). Adenovirus Biology, Recombinant Adenovirus, and Adenovirus Usage in Gene Therapy. Viruses, 13.","DOI":"10.3390\/v13122502"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.hoc.2017.06.007","article-title":"Nonintegrating Gene Therapy Vectors","volume":"31","author":"Athanasopoulos","year":"2017","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1153728","DOI":"10.3389\/fmicb.2023.1153728","article-title":"Genetic characterization of human adenoviruses in patients using metagenomic next-generation sequencing in Hubei, China, from 2018 to 2019","volume":"14","author":"Fang","year":"2023","journal-title":"Front. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"866","DOI":"10.52586\/4993","article-title":"Tropism and transduction of oncolytic adenovirus vectors in prostate cancer therapy","volume":"26","author":"Wu","year":"2021","journal-title":"Front. Biosci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Crenshaw, B.J., Jones, L.B., Bell, C.R., Kumar, S., and Matthews, Q.L. (2019). Perspective on Adenoviruses: Epidemiology, Pathogenicity, and Gene Therapy. Biomedicines, 7.","DOI":"10.3390\/biomedicines7030061"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kulanayake, S., and Tikoo, S.K. (2021). Adenovirus Core Proteins: Structure and Function. Viruses, 13.","DOI":"10.3390\/v13030388"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rosewell Shaw, A., Porter, C., Biegert, G., Jatta, L., and Suzuki, M. (2022). HydrAd: A Helper-Dependent Adenovirus Targeting Multiple Immune Pathways for Cancer Immunotherapy. Cancers, 14.","DOI":"10.3390\/cancers14112769"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mantwill, K., Klein, F.G., Wang, D., Hindupur, S.V., Ehrenfeld, M., Holm, P.S., and Nawroth, R. (2021). Concepts in Oncolytic Adenovirus Therapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910522"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"127","DOI":"10.2174\/1566523220999200731003206","article-title":"Applications of Recombinant Adenovirus-p53 Gene Therapy for Cancers in the Clinic in China","volume":"20","author":"Xia","year":"2020","journal-title":"Curr. Gene Ther."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yang, K., Feng, S., and Luo, Z. (2022). Oncolytic Adenovirus, a New Treatment Strategy for Prostate Cancer. Biomedicines, 10.","DOI":"10.3390\/biomedicines10123262"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"The Medical Letter, Inc. (2023). In brief: Adstiladrin\u2014A gene therapy for bladder cancer. Med. Lett. Drugs Ther., 65, e40\u2013e41.","DOI":"10.58347\/tml.2023.1671e"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/s13287-019-1268-z","article-title":"Mesenchymal stem cell-mediated delivery of therapeutic adenoviral vectors to prostate cancer","volume":"10","author":"Muhammad","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2147\/OV.S155946","article-title":"Oncolytic adenovirus Ad657 for systemic virotherapy against prostate cancer","volume":"7","author":"Nguyen","year":"2018","journal-title":"Oncolytic Virother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41417-018-0043-0","article-title":"The effect of gene therapy on postoperative recurrence of small hepatocellular carcinoma (less than 5cm)","volume":"26","author":"Meng","year":"2019","journal-title":"Cancer Gene Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5317","DOI":"10.1039\/D0BM00681E","article-title":"Biosilicified oncolytic adenovirus for cancer viral gene therapy","volume":"8","author":"Kong","year":"2020","journal-title":"Biomater. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.7150\/jca.51434","article-title":"Cytokine-induced killer cells carrying recombinant oncolytic adenovirus expressing p21Ras scFv inhibited liver cancer","volume":"12","author":"Dai","year":"2021","journal-title":"J. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jconrel.2017.05.017","article-title":"Aptamer-mediated gene therapy enhanced antitumor activity against human hepatocellular carcinoma in vitro and in vivo","volume":"258","author":"Xiao","year":"2017","journal-title":"J. Control Release"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e003645","DOI":"10.1136\/jitc-2021-003645","article-title":"Safety and efficacy of the tumor-selective adenovirus enadenotucirev with or without paclitaxel in platinum-resistant ovarian cancer: A phase 1 clinical trial","volume":"9","author":"Moreno","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.ygyno.2021.02.014","article-title":"Utilizing an interim futility analysis of the OVAL study (VB-111-701\/GOG 3018) for potential reduction of risk: A phase III, double blind, randomized controlled trial of ofranergene obadenovec (VB-111) and weekly paclitaxel in patients with platinum resistant ovarian cancer","volume":"161","author":"Arend","year":"2021","journal-title":"Gynecol. Oncol."},{"key":"ref_47","first-page":"4853","article-title":"The effects of interleukin 2 and rAd-p53 as a treatment for glioblastoma","volume":"17","author":"Qiao","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1089\/hum.2017.206","article-title":"Treatment of Uterine Sarcoma with rAd-p53 (Gendicine) Followed by Chemotherapy: Clinical Study of TP53 Gene Therapy","volume":"29","author":"Xia","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6453","DOI":"10.1038\/s41467-022-33834-4","article-title":"A phase I study of an adenoviral vector delivering a MUC1\/CD40-ligand fusion protein in patients with advanced adenocarcinoma","volume":"13","author":"Tan","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3791","DOI":"10.1158\/1078-0432.CCR-15-2133","article-title":"Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFN\u03b1 Combined with Chemotherapy","volume":"22","author":"Sterman","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1006\/mthe.2002.0658","article-title":"Systemic interleukin-6 responses following administration of adenovirus gene transfer vectors to humans by different routes","volume":"6","author":"McKinney","year":"2002","journal-title":"Mol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.1002\/1873-3468.13696","article-title":"Innate immunity to adenovirus: Lessons from mice","volume":"593","author":"Atasheva","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1556\/EuJMI.1.2011.4.3","article-title":"Adenovirus-triggered innate signalling pathways","volume":"1","author":"Fejer","year":"2011","journal-title":"Eur. J. Microbiol. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10440","DOI":"10.1073\/pnas.1806314115","article-title":"TRIM21 mediates antibody inhibition of adenovirus-based gene delivery and vaccination","volume":"115","author":"Bottermann","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4035","DOI":"10.1128\/JVI.02160-10","article-title":"Adenovirus virus-associated RNAs induce type I interferon expression through a RIG-I-mediated pathway","volume":"85","author":"Minamitani","year":"2011","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17286","DOI":"10.1073\/pnas.1009823107","article-title":"Induction of type I interferon by adenovirus-encoded small RNAs","volume":"107","author":"Yamaguchi","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Jiang, H., Clise-Dwyer, K., Ruisaard, K.E., Fan, X., Tian, W., Gumin, J., Lamfers, M.L., Kleijn, A., Lang, F.F., and Yung, W.K. (2014). Delta-24-RGD oncolytic adenovirus elicits anti-glioma immunity in an immunocompetent mouse model. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097407"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s42003-022-03041-4","article-title":"Carvedilol targets \u03b2-arrestins to rewire innate immunity and improve oncolytic adenoviral therapy","volume":"5","author":"Hoare","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Wang, W.C., Sayedahmed, E.E., and Mittal, S.K. (2022). Significance of Preexisting Vector Immunity and Activation of Innate Responses for Adenoviral Vector-Based Therapy. Viruses, 14.","DOI":"10.3390\/v14122727"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"108297","DOI":"10.1016\/j.celrep.2020.108297","article-title":"MYSM1 Represses Innate Immunity and Autoimmunity through Suppressing the cGAS-STING Pathway","volume":"33","author":"Tian","year":"2020","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Kreppel, F., and Hagedorn, C. (2021). Capsid and Genome Modification Strategies to Reduce the Immunogenicity of Adenoviral Vectors. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052417"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/978-1-0716-0795-4_18","article-title":"Surface Modification of Adenovirus Vector to Improve Immunogenicity and Tropism","volume":"2183","author":"Gabal","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Gentile, C.M., Borovjagin, A.V., Richter, J.R., Jani, A.H., Wu, H., Zinn, K.R., and Warram, J.M. (2019). Genetic strategy to decrease complement activation with adenoviral therapies. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215226"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"eabc6659","DOI":"10.1126\/scitranslmed.abc6659","article-title":"Systemic cancer therapy with engineered adenovirus that evades innate immunity","volume":"12","author":"Atasheva","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"113","DOI":"10.18632\/oncotarget.231","article-title":"The challenge for gene therapy: Innate immune response to adenoviruses","volume":"2","author":"Thaci","year":"2011","journal-title":"Oncotarget"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1021\/acs.nanolett.9b00145","article-title":"Genetically Engineered Cell Membrane Nanovesicles for Oncolytic Adenovirus Delivery: A Versatile Platform for Cancer Virotherapy","volume":"19","author":"Lv","year":"2019","journal-title":"Nano Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e58","DOI":"10.1002\/cpmo.58","article-title":"Viral Vectors for Gene Transfer","volume":"8","author":"Chen","year":"2018","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"13133","DOI":"10.1128\/JVI.05407-11","article-title":"Adeno-associated virus activates an innate immune response in normal human cells but not in osteosarcoma cells","volume":"85","author":"Laredj","year":"2011","journal-title":"J. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Issa, S.S., Shaimardanova, A.A., Solovyeva, V.V., and Rizvanov, A.A. (2023). Various AAV Serotypes and Their Applications in Gene Therapy: An Overview. Cells, 12.","DOI":"10.3390\/cells12050785"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/rmv.1762","article-title":"Adeno-associated virus (AAV) vectors in gene therapy: Immune challenges and strategies to circumvent them","volume":"23","author":"Hareendran","year":"2013","journal-title":"Rev. Med. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1086\/595830","article-title":"Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses","volume":"199","author":"Calcedo","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1146\/annurev-virology-092818-015530","article-title":"Recombinant Adeno-Associated Virus Gene Therapy in Light of Luxturna (and Zolgensma and Glybera): Where Are We, and How Did We Get Here?","volume":"6","author":"Keeler","year":"2019","journal-title":"Annu. Rev. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1097\/ICU.0000000000000660","article-title":"Gene therapy beyond luxturna: A new horizon of the treatment for inherited retinal disease","volume":"31","author":"Prado","year":"2020","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1056\/NEJMra1706910","article-title":"Gene Therapy","volume":"381","author":"High","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1016\/j.ymthe.2020.06.001","article-title":"Long-Term Follow-Up of the First in Human Intravascular Delivery of AAV for Gene Transfer: AAV2-hFIX16 for Severe Hemophilia B","volume":"28","author":"George","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1056\/NEJMoa2104205","article-title":"Multiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A","volume":"385","author":"George","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1182\/blood-2017-09-804419","article-title":"Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B","volume":"131","author":"Miesbach","year":"2018","journal-title":"Blood"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1056\/NEJMoa1908490","article-title":"Multiyear Follow-up of AAV5-hFVIII-SQ Gene Therapy for Hemophilia A","volume":"382","author":"Pasi","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1056\/NEJMoa1407309","article-title":"Long-term safety and efficacy of factor IX gene therapy in hemophilia B","volume":"371","author":"Nathwani","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-1-61779-370-7_6","article-title":"AAV-mediated liver-directed gene therapy","volume":"807","author":"Sands","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1056\/NEJMoa1108046","article-title":"Adenovirus-associated virus vector-mediated gene transfer in hemophilia B","volume":"365","author":"Nathwani","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0140-6736(17)31868-8","article-title":"Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: A randomised, controlled, open-label, phase 3 trial","volume":"390","author":"Russell","year":"2017","journal-title":"Lancet"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.ymthe.2019.12.010","article-title":"AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer","volume":"28","author":"Verdera","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1056\/NEJMoa0802315","article-title":"Safety and efficacy of gene transfer for Leber\u2019s congenital amaurosis","volume":"358","author":"Maguire","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1001\/jamaophthalmol.2020.1032","article-title":"Safety and Vision Outcomes of Subretinal Gene Therapy Targeting Cone Photoreceptors in Achromatopsia: A Nonrandomized Controlled Trial","volume":"138","author":"Fischer","year":"2020","journal-title":"JAMA Ophthalmol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1089\/hum.2018.014","article-title":"Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy","volume":"29","author":"Pennesi","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1016\/S0140-6736(07)60982-9","article-title":"Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson\u2019s disease: An open label, phase I trial","volume":"369","author":"Kaplitt","year":"2007","journal-title":"Lancet"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"S212","DOI":"10.1002\/jgm.506","article-title":"Recombinant AAV-mediated gene delivery to the central nervous system","volume":"6","author":"Tenenbaum","year":"2004","journal-title":"J. Gene Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1089\/hum.2019.367","article-title":"Postmortem Analysis in a Clinical Trial of AAV2-NGF Gene Therapy for Alzheimer\u2019s Disease Identifies a Need for Improved Vector Delivery","volume":"31","author":"Castle","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4251","DOI":"10.1038\/s41467-021-24524-8","article-title":"Gene therapy for aromatic L-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons","volume":"12","author":"Pearson","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.omtm.2019.03.002","article-title":"AAV5-miHTT Gene Therapy Demonstrates Sustained Huntingtin Lowering and Functional Improvement in Huntington Disease Mouse Models","volume":"13","author":"Spronck","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.omtm.2019.10.008","article-title":"Development of an AAV-Based MicroRNA Gene Therapy to Treat Machado-Joseph Disease","volume":"15","author":"Martier","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jconrel.2016.09.011","article-title":"Gene therapy for the CNS using AAVs: The impact of systemic delivery by AAV9","volume":"241","author":"Saraiva","year":"2016","journal-title":"J. Control Release"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.bbrc.2020.07.031","article-title":"AAV9-DOK7 gene therapy reduces disease severity in Smn(2B\/-) SMA model mice","volume":"530","author":"Kaifer","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1001\/jamaneurol.2020.1484","article-title":"Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children with Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial","volume":"77","author":"Mendell","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e1852","DOI":"10.1212\/WNL.0000000000007319","article-title":"X-linked myotubular myopathy: A prospective international natural history study","volume":"92","author":"Annoussamy","year":"2019","journal-title":"Neurology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e143285","DOI":"10.1172\/jci.insight.143285","article-title":"VEGFA165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss","volume":"6","author":"Zhang","year":"2021","journal-title":"JCI Insight"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ymthe.2016.12.010","article-title":"Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV","volume":"25","author":"Gyorgy","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.omtm.2018.11.003","article-title":"Gene Transfer with AAV9-PHP.B Rescues Hearing in a Mouse Model of Usher Syndrome 3A and Transduces Hair Cells in a Non-human Primate","volume":"13","author":"Meijer","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"eabd3438","DOI":"10.1126\/scitranslmed.abd3438","article-title":"Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses","volume":"13","author":"Chan","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41576-019-0205-4","article-title":"Engineering adeno-associated virus vectors for gene therapy","volume":"21","author":"Li","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1038\/mt.2010.124","article-title":"Recognition of virus infection and innate host responses to viral gene therapy vectors","volume":"18","author":"Shayakhmetov","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1172\/JCI37607","article-title":"The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice","volume":"119","author":"Zhu","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"6459","DOI":"10.1182\/blood-2010-10-314518","article-title":"The genome of self-complementary adeno-associated viral vectors increases Toll-like receptor 9-dependent innate immune responses in the liver","volume":"117","author":"Martino","year":"2011","journal-title":"Blood"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e20220759","DOI":"10.1084\/jem.20220759","article-title":"Monocyte-derived macrophages aggravate pulmonary vasculitis via cGAS\/STING\/IFN-mediated nucleic acid sensing","volume":"219","author":"Kessler","year":"2022","journal-title":"J. Exp. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e120474","DOI":"10.1172\/jci.insight.120474","article-title":"Double-stranded RNA innate immune response activation from long-term adeno-associated virus vector transduction","volume":"3","author":"Shao","year":"2018","journal-title":"JCI Insight"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"670","DOI":"10.3389\/fimmu.2020.00670","article-title":"Human Immune Responses to Adeno-Associated Virus (AAV) Vectors","volume":"11","author":"Ronzitti","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/mt.2008.297","article-title":"Transient pretreatment with glucocorticoid ablates innate toxicity of systemically delivered adenoviral vectors without reducing efficacy","volume":"17","author":"Seregin","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/978-3-030-27378-1_27","article-title":"Innate Immune Response Following AAV Administration","volume":"1185","author":"Dauletbekov","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/nbt1182","article-title":"Directed evolution of adeno-associated virus yields enhanced gene delivery vectors","volume":"24","author":"Maheshri","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"672449","DOI":"10.3389\/fimmu.2021.672449","article-title":"Effect of CpG Depletion of Vector Genome on CD8(+) T Cell Responses in AAV Gene Therapy","volume":"12","author":"Bertolini","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Munis, A.M. (2020). Gene Therapy Applications of Non-Human Lentiviral Vectors. Viruses, 12.","DOI":"10.3390\/v12101106"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"de Pablo-Maiso, L., Domenech, A., Echeverria, I., Gomez-Arrebola, C., de Andres, D., Rosati, S., Gomez-Lucia, E., and Reina, R. (2018). Prospects in Innate Immune Responses as Potential Control Strategies against Non-Primate Lentiviruses. Viruses, 10.","DOI":"10.3390\/v10080435"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41392-021-00487-6","article-title":"Viral vector platforms within the gene therapy landscape","volume":"6","author":"Bulcha","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Perry, C., and Rayat, A. (2021). Lentiviral Vector Bioprocessing. Viruses, 13.","DOI":"10.3390\/v13020268"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.omtm.2019.11.021","article-title":"Lentiviral Vector Production Titer Is Not Limited in HEK293T by Induced Intracellular Innate Immunity","volume":"17","author":"Ferreira","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41591-019-0735-5","article-title":"Lentiviral gene therapy for X-linked chronic granulomatous disease","volume":"26","author":"Kohn","year":"2020","journal-title":"Nat. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1056\/NEJMoa1705342","article-title":"Gene Therapy in Patients with Transfusion-Dependent beta-Thalassemia","volume":"378","author":"Thompson","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41591-021-01650-w","article-title":"Long-term outcomes of lentiviral gene therapy for the \u03b2-hemoglobinopathies: The HGB-205 trial","volume":"28","author":"Magrin","year":"2022","journal-title":"Nat. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1056\/NEJMoa1815408","article-title":"Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1","volume":"380","author":"Mamcarz","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1056\/NEJMoa2206575","article-title":"Lentiviral Gene Therapy for Artemis-Deficient SCID","volume":"387","author":"Cowan","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1056\/NEJMoa1700554","article-title":"Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy","volume":"377","author":"Eichler","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1056\/NEJMoa2106596","article-title":"Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome","volume":"385","author":"Gentner","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/S0140-6736(16)30374-9","article-title":"Lentiviral haemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy: An ad-hoc analysis of a non-randomised, open-label, phase 1\/2 trial","volume":"388","author":"Sessa","year":"2016","journal-title":"Lancet"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/ajh.26160","article-title":"Combination of CD19 and CD22 CAR-T cell therapy in relapsed B-cell acute lymphoblastic leukemia after allogeneic transplantation","volume":"96","author":"Liu","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1172\/JCI126397","article-title":"B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma","volume":"129","author":"Cohen","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"5842","DOI":"10.1016\/j.vaccine.2017.09.017","article-title":"Breast cancer vaccines delivered by dendritic cell-targeted lentivectors induce potent antitumor immune responses and protect mice from mammary tumor growth","volume":"35","author":"Bryson","year":"2017","journal-title":"Vaccine"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"120793","DOI":"10.1016\/j.biomaterials.2021.120793","article-title":"Systemic delivery of CRISPR\/Cas9 to hepatic tumors for cancer treatment using altered tropism of lentiviral vector","volume":"272","author":"Lee","year":"2021","journal-title":"Biomaterials"},{"key":"ref_129","first-page":"2015","article-title":"Lentiviral Vector-mediated Gene Transfer in Human Bladder Cancer Cell Lines","volume":"38","author":"Matsunaga","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.omtm.2021.04.016","article-title":"Non-genotoxic conditioning facilitates hematopoietic stem cell gene therapy for hemophilia A using bioengineered factor VIII","volume":"21","author":"Russell","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.omtm.2021.10.015","article-title":"Efficient and safe correction of hemophilia A by lentiviral vector-transduced BOECs in an implantable device","volume":"23","author":"Olgasi","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1038\/s41467-022-30102-3","article-title":"Liver-directed lentiviral gene therapy corrects hemophilia A mice and achieves normal-range factor VIII activity in non-human primates","volume":"13","author":"Milani","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1002\/jcp.29861","article-title":"In vivo enrichment of genetically manipulated platelets for murine hemophilia B gene therapy","volume":"236","author":"Chen","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.3233\/JAD-200757","article-title":"Lentivirus-Mediated Expression of Human Secreted Amyloid Precursor Protein-Alpha Promotes Long-Term Induction of Neuroprotective Genes and Pathways in a Mouse Model of Alzheimer\u2019s Disease","volume":"79","author":"Ryan","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.neurobiolaging.2019.02.003","article-title":"Lentiviral vector-mediated overexpression of Klotho in the brain improves Alzheimer\u2019s disease-like pathology and cognitive deficits in mice","volume":"78","author":"Zeng","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Van Kampen, J.M., and Kay, D.G. (2017). Progranulin gene delivery reduces plaque burden and synaptic atrophy in a mouse model of Alzheimer\u2019s disease. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182896"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/mt.2014.164","article-title":"Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia","volume":"23","author":"Wang","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1182\/blood-2006-10-049312","article-title":"In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance","volume":"109","author":"Brown","year":"2007","journal-title":"Blood"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"716927","DOI":"10.3389\/fimmu.2021.716927","article-title":"Dodging the Host Interferon-Stimulated Gene Mediated Innate Immunity by HIV-1: A Brief Update on Intrinsic Mechanisms and Counter-Mechanisms","volume":"12","author":"Chintala","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.15252\/emmm.201707922","article-title":"Lentiviral vectors escape innate sensing but trigger p53 in human hematopoietic stem and progenitor cells","volume":"9","author":"Piras","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1089\/hum.2015.036","article-title":"Cellular innate immunity and restriction of viral infection: Implications for lentiviral gene therapy in human hematopoietic cells","volume":"26","author":"Naldini","year":"2015","journal-title":"Hum. Gene Ther."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Coroadinha, A.S. (2023). Host Cell Restriction Factors Blocking Efficient Vector Transduction: Challenges in Lentiviral and Adeno-Associated Vector Based Gene Therapies. Cells, 12.","DOI":"10.3390\/cells12050732"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"103802","DOI":"10.1016\/j.cellimm.2018.04.012","article-title":"Modulation of immune responses in lentiviral vector-mediated gene transfer","volume":"342","author":"Annoni","year":"2019","journal-title":"Cell Immunol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s41418-021-00849-1","article-title":"The Hippo signaling component LATS2 enhances innate immunity to inhibit HIV-1 infection through PQBP1-cGAS pathway","volume":"29","author":"He","year":"2022","journal-title":"Cell Death Differ."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3389\/fcimb.2019.00069","article-title":"Application of CRISPR\/Cas9-Based Gene Editing in HIV-1\/AIDS Therapy","volume":"9","author":"Xiao","year":"2019","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"eaav7325","DOI":"10.1126\/scitranslmed.aav7325","article-title":"Phagocytosis-shielded lentiviral vectors improve liver gene therapy in nonhuman primates","volume":"11","author":"Milani","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1039\/D1TB01815A","article-title":"Less phagocytosis of viral vectors by tethering with CD47 ectodomain","volume":"10","author":"Alyami","year":"2021","journal-title":"J. Mater. Chem. B"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1089\/hum.2012.080","article-title":"Inhibition of intracellular antiviral defense mechanisms augments lentiviral transduction of human natural killer cells: Implications for gene therapy","volume":"23","author":"Sutlu","year":"2012","journal-title":"Hum. Gene Ther."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.stem.2018.10.008","article-title":"Cyclosporine H Overcomes Innate Immune Restrictions to Improve Lentiviral Transduction and Gene Editing in Human Hematopoietic Stem Cells","volume":"23","author":"Petrillo","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1038\/mt.2012.150","article-title":"A TLR and non-TLR mediated innate response to lentiviruses restricts hepatocyte entry and can be ameliorated by pharmacological blockade","volume":"20","author":"Agudo","year":"2012","journal-title":"Mol. 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