کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5537329 | 1402330 | 2016 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Intramuscular administration of AAV overcomes pre-existing neutralizing antibodies in rhesus macaques
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
AATrecombinase activation geneRAGnAbsSIVIVIgNHPAAVCTLIACUCmAbalpha-1-antitrypsin - آلفا 1-آنتی تیپسینMonoclonal antibody - آنتی بادی مونوکلونالNeutralizing antibodies - آنتی بادیهای ناتریالImmunoadhesin - ایمونوادشینIntravenous immunoglobulin - اﯾﻤﻮﻧﻮﮔﻠﻮﺑﻮﻟﯿﻦ ورﯾﺪیVector - بردارEnzyme-linked immunosorbent assay - تست الیزاELISA - تست الیزاIntravenous - داخل وریدیInstitutional Animal Care and Use Committee - سازمان مراقبت و مراقبت از حیواناتcytomegalovirus - سیتومگالوویروسCMV - سیتومگالوویروسSHIV - شویIntramuscular - عضلانیMuscle - عضلهcytotoxic T lymphocyte - لنفوسیت T سیتوتوکسیکFirefly luciferase - لوسیفراز فیرفیلیknockout - ناکاوتnon-human primate - نخستیسانان غیرانسانیHIV - ویروس نقص ایمنی انسانی human immunodeficiency virus - ویروس نقص ایمنی انسانیsimian-human immunodeficiency virus - ویروس نقص ایمنی بدن انسانSimian immunodeficiency virus - ویروس کمبود ایمنی سیمانیadeno-associated viral - ویروسی مرتبط با آدنوAntibody - پادتَن یا آنتیبادی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Intramuscular administration of AAV overcomes pre-existing neutralizing antibodies in rhesus macaques Intramuscular administration of AAV overcomes pre-existing neutralizing antibodies in rhesus macaques](/preview/png/5537329.png)
چکیده انگلیسی
The seroprevalence of neutralizing antibodies (NAbs) to adeno-associated viral (AAV) vector capsids may preclude a percentage of the population from receiving gene therapy, particularly following systemic vector administration. We hypothesized that the use of intramuscular (IM) administration of AAV vectors might circumvent this issue. IM injections were used to administer AAV8 vectors expressing either secreted or non-secreted transgenes into mice and the influence of NAbs supplied by pre-administration of pooled human IgG on transgene expression was evaluated. We then studied the impact of naturally occurring pre-existing AAV8 NAbs on expression of a secreted transgene following IM vector delivery in rhesus macaques. Finally, we evaluated the ability to readminister AAV vectors via IM injections in rhesus macaques. In mice, the presence of AAV8 NAbs had no effect on gene expression in the injected skeletal muscle. However, liver transgene expression following hepatic distribution of the vector was ablated. In rhesus macaques, naturally occurring pre-existing AAV8 NAb titers of ⩽1:160 had no effect on expression levels of a secreted transgene after IM delivery of the vector. Additionally, readministration of AAV vectors was possible by IM injection into the previously injected muscle groups, with no effect on transgene expression by the original vector. Therefore, the presence of pre-existing NAbs in the human population should not preclude subjects from receiving gene therapy by IM administration of the vector so long as sufficient levels of secreted transgene expression can be produced without the involvement of liver.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vaccine - Volume 34, Issue 50, 7 December 2016, Pages 6323-6329
Journal: Vaccine - Volume 34, Issue 50, 7 December 2016, Pages 6323-6329
نویسندگان
Jenny A. Greig, Roberto Calcedo, Rebecca L. Grant, Hui Peng, C. Angelica Medina-Jaszek, Omua Ahonkhai, Qiuyue Qin, Soumitra Roy, Anna P. Tretiakova, James M. Wilson,