{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:15:28Z","timestamp":1792732528045,"version":"4.5.0"},"reference-count":98,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,9,10]],"date-time":"2013-09-10T00:00:00Z","timestamp":1378771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reviews in Medical Virology"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                  <jats:p>AAV\u2010based gene transfer protocols have shown remarkable success when directed to immune\u2010privileged sites such as for retinal disorders like Lebers congenital amaurosis. In contrast, AAV\u2010mediated gene transfer into liver or muscle tissue for diseases such as hemophilia B, \u03b11 anti\u2010trypsin deficiency and muscular dystrophy has demonstrated a decline in gene transfer efficacy over time. It is now known that in humans, AAV triggers specific pathways that recruit immune sensors. These factors initiate an immediate reaction against either the viral capsid or the vector encoded protein as part of innate immune response or to produce a more specific adaptive response that generates immunological memory. The vector\u2010transduced cells are then rapidly destroyed due to this immune activation. However, unlike other viral vectors, AAV is not immunogenic in murine models. Its immunogenicity becomes apparent only in large animal models and human subjects. Moreover, humans are natural hosts to AAV and exhibit a high seroprevalence against AAV vectors. This limits the widespread application of AAV vectors into patients with pre\u2010existing neutralising antibodies or memory T cells. To address these issues, various strategies are being tested. Alternate serotype vectors (AAV1\u201010), efficient expression cassettes, specific tissue targeting, immune\u2010suppression and engineered capsid variants are some approaches proposed to minimise this immune stimulation. In this review, we have summarised the nature of the immune response documented against AAV in various pre\u2010clinical and clinical settings and have further discussed the strategies to evade them. Copyright \u00a9 2013 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/rmv.1762","type":"journal-article","created":{"date-parts":[[2013,9,11]],"date-time":"2013-09-11T06:06:29Z","timestamp":1378879589000},"page":"399-413","source":"Crossref","is-referenced-by-count":104,"title":["Adeno\u2010associated virus (AAV) vectors in gene therapy: immune challenges and strategies to circumvent them"],"prefix":"10.1002","volume":"23","author":[{"given":"Sangeetha","family":"Hareendran","sequence":"first","affiliation":[{"name":"Centre for Stem Cell Research Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balaji","family":"Balakrishnan","sequence":"additional","affiliation":[{"name":"Department of Hematology Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwaipayan","family":"Sen","sequence":"additional","affiliation":[{"name":"Department of Hematology Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Kumar","sequence":"additional","affiliation":[{"name":"Centre for Stem Cell Research Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alok","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Centre for Stem Cell Research Christian Medical College  Vellore Tamil Nadu India"},{"name":"Department of Hematology Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giridhara R.","family":"Jayandharan","sequence":"additional","affiliation":[{"name":"Centre for Stem Cell Research Christian Medical College  Vellore Tamil Nadu India"},{"name":"Department of Hematology Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.287"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652308786847996"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652311795684740"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.9.4580-4590.2002"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00008-08"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2009.064"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2988"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.76"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1000228"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2009.182"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1108046"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1358"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1549"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.885"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904514106"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-167510"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1128\/JVI.72.4.2945-2954.1998","article-title":"Cytotoxic T\u2010lymphocyte target proteins and their major histocompatibility complex class I restriction in response to adenovirus vectors delivered to mouse liver","volume":"72","author":"Jooss K","year":"1998","journal-title":"Journal of Virology"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2008.54"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.17.8003-8010.2000"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.1128\/JVI.72.5.4212-4223.1998","article-title":"Transduction of dendritic cells by DNA viral vectors directs the immune response to transgene products in muscle fibers","volume":"72","author":"Jooss K","year":"1998","journal-title":"Journal of Virology"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01990-07"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.6.2777-2785.2000"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-314518"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012753108"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053845"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00046-08"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI37607"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00194"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302527"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2012.6"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.074134"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/16729"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2010.02504.x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.26.931"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.8.3071-3084.2006"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.2.1438-1445.1998"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000922"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/415092a"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00611-0"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.12.6799-6810.2003"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.182412299"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1086\/595830"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.035113-0"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-02-0495"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2012.10.003"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2011.031"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.05107-11"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200620"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1601"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.01.001"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66611"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36891"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00529-07"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00675-12"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902269106"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803965"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1445"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.159"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23043"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300090"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.81"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.40"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802315"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2008.107"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70039-4"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28349"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-181479"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.25"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.33"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2011.64"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-12-5115"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00199"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037671"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300377"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034684"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.257"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2070"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1256"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2003.11.015"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-10-4035"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2010.157"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.20562"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2005.07.019"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802866105"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.4.1761-1766.2000"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302123"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00204"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.19.9281-9293.2000"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.2.821-834.2006"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.184"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1182"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-0016(03)00123-0"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2009.10.021"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-10-460733"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1089\/hgtb.2012.194"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1089\/hgtb.2012.195"},{"key":"e_1_2_8_98_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.301"},{"key":"e_1_2_8_99_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.12.6381-6388.2004"}],"container-title":["Reviews in Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Frmv.1762","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rmv.1762","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T14:34:24Z","timestamp":1697380464000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/rmv.1762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9,10]]},"references-count":98,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1002\/rmv.1762"],"URL":"https:\/\/doi.org\/10.1002\/rmv.1762","archive":["Portico"],"relation":{},"ISSN":["1052-9276","1099-1654"],"issn-type":[{"value":"1052-9276","type":"print"},{"value":"1099-1654","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9,10]]}}}