A comprehensive atlas of AAV tropism in the mouse

被引：0

作者：

Walkey, Christopher J. ^{[1
,10
]}

Snow, Kathy J. ^{[2
]}

Bulcha, Jote ^{[3
,4
,5
,14
]}

Cox, Aaron R. ^{[6
,15
]}

Martinez, Alexa E. ^{[1
,16
]}

Ljungberg, M. Cecilia ^{[7
,8
]}

Lanza, Denise G. ^{[9
]}

De Giorgi, Marco ^{[1
]}

Chuecos, Marcel A. ^{[1
]}

Alves-Bezerra, Michele ^{[1
,17
]}

Suarez, Carlos Flores ^{[1
,18
]}

Hartig, Sean M. ^{[6
,10
]}

Hilsenbeck, Susan G. ^{[11
]}

Hsu, Chih-Wei ^{[1
]}

Saville, Ethan ^{[2
]}

Gaitan, Yaned ^{[2
]}

Duryea, Jeff ^{[2
]}

Hannigan, Seth ^{[2
]}

Dickinson, Mary E. ^{[1
,19
]}

Mirochnitchenko, Oleg ^{[12
]}

Wang, Dan ^{[3
,4
,13
]}

Lutz, Cathleen M. ^{[2
]}

Heaney, Jason D. ^{[9
]}

Gao, Guangping ^{[3
,4
,5
]}

Murray, Stephen A. ^{[2
]}

Lagor, William R. ^{[1
]}

机构：

[1] Baylor Coll Med, Dept Integrat Physiol, Houston, TX 77030 USA

[2] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA

[3] Univ Massachusetts, Med Sch, Horae Gene Therapy Ctr, Worcester, MA 01605 USA

[4] Univ Massachusetts, Dept Microbiol & Physiol Syst, Med Sch, Worcester, MA 01605 USA

[5] Univ Massachusetts, Med Sch, Li Weibo Inst Rare Dis Res, Worcester, MA 01605 USA

[6] Baylor Coll Med, Dept Med, Sect Diabet Endocrinol & Metab, Houston, TX 77030 USA

[7] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

[8] Texas Childrens Hosp, Duncan Neurol Res Inst, Houston, TX 77030 USA

[9] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX USA

[10] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[11] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Houston, TX USA

[12] NIH, Off Res Infrastructure Programs, Div Program Coordinat Planning & Strateg Initiat, Off Director, Bethesda, MD USA

[13] Univ Massachusetts, Med Sch, RNA Therapeut Inst, Worcester, MA USA

[14] 4D Mol Therapeut, Emeryville, CA 94608 USA

[15] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA

[16] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA

[17] Univ Cadiz, Biomed Res & Innovat Inst Cadiz INiB, Dept Biomed Biotechnol & Publ Hlth, Cadiz 11002, Spain

[18] Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

[19] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA

来源：

MOLECULAR THERAPY | 2025年 / 33卷 / 03期

关键词：

GENE-THERAPY VECTOR; ADENOASSOCIATED VIRUS SEROTYPES; DIRECTED EVOLUTION; IN-VIVO; GERMLINE TRANSMISSION; LIVER TRANSDUCTION; VIRAL GENE; BETA-CELLS; WILD-TYPE; IDENTIFICATION;

D O I：

10.1016/j.ymthe.2025.01.041

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Gene therapy with adeno-associated virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of 10 naturally occurring AAV serotypes AAVrh8, AAVrh10, and AAVrh74) following systemic delivery into male and female mice. A transgene-expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence. Cre-driven activation of tdTomato fluorescence offered superior sensitivity for transduced cells. All serotypes except AAV3B and AAV4 had high liver tropism. Fluorescence activation revealed transduction of unexpected tissues, including adrenals, testes, and ovaries. Rare transduced cells within tissues were also readily visualized. Biodistribution of AAV genomes correlated with fluorescence, except in immune tissues. AAV4 was found to have a pan-endothelial tropism while also targeting pancreatic beta cells. This public resource enables selection of the best AAV serotypes for basic science and preclinical applications in mice.

引用

页码：1282 / 1299

页数：18

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