Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain

被引：31

作者：

Chuapoco, Miguel R. ^{[1
,2
]}

Flytzanis, Nicholas C. ^{[1
,10
]}

Goeden, Nick ^{[1
,10
]}

Octeau, J. Christopher ^{[10
]}

Roxas, Kristina M. ^{[10
]}

Chan, Ken Y. ^{[1
,11
]}

Scherrer, Jon ^{[10
]}

Winchester, Janet ^{[10
]}

Blackburn, Roy J. ^{[10
]}

Campos, Lillian J. ^{[2
,3
,4
]}

Man, Kwun Nok Mimi ^{[5
]}

Sun, Junqing ^{[5
]}

Chen, Xinhong ^{[1
,2
]}

Lefevre, Arthur ^{[6
]}

Singh, Vikram Pal ^{[6
]}

Arokiaraj, Cynthia M. ^{[1
,2
]}

Shay, Timothy F. ^{[1
]}

Vendemiatti, Julia ^{[1
]}

Jang, Min J. ^{[1
,2
]}

Mich, John K. ^{[7
]}

Bishaw, Yemeserach ^{[7
]}

Gore, Bryan B. ^{[7
]}

Omstead, Victoria ^{[7
]}

Taskin, Naz ^{[7
]}

Weed, Natalie ^{[7
]}

Levi, Boaz P. ^{[7
]}

Ting, Jonathan T. ^{[7
,8
]}

Miller, Cory T. ^{[6
]}

Deverman, Benjamin E. ^{[1
,11
]}

Pickel, James ^{[9
]}

Tian, Lin ^{[2
,5
]}

Fox, Andrew S. ^{[2
,3
,4
]}

Gradinaru, Viviana ^{[1
,2
]}

机构：

[1] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA

[2] Aligning Sci Parkinsons ASAP Collaborat Res Netwo, Chevy Chase, MD 20815 USA

[3] Univ Calif Davis, Dept Psychol, Davis, CA USA

[4] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA USA

[5] Univ Calif Davis, Dept Biochem & Mol Med, Davis, CA USA

[6] Univ Calif San Diego, Cort Syst & Behav Lab, San Diego, CA USA

[7] Allen Inst Brain Sci, Seattle, WA USA

[8] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA USA

[9] NIMH, NIH, Bethesda, MD USA

[10] Capsida Biotherapeut, Thousand Oaks, CA 91320 USA

[11] MIT, Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA

来源：

NATURE NANOTECHNOLOGY | 2023年 / 18卷 / 10期

基金：

美国国家卫生研究院;

关键词：

CENTRAL-NERVOUS-SYSTEM; VIRUS VECTOR; IN-VIVO; DELIVERY; EXPRESSION; BARRIER; LIVER; STRATEGIES; TOXICOLOGY; EVOLUTION;

D O I：

10.1038/s41565-023-01419-x

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Crossing the blood-brain barrier in primates is a major obstacle for gene delivery to the brain. Adeno-associated viruses (AAVs) promise robust, non-invasive gene delivery from the bloodstream to the brain. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates. Here we report on AAV.CAP-Mac, an engineered variant identified by screening in adult marmosets and newborn macaques, which has improved delivery efficiency in the brains of multiple non-human primate species: marmoset, rhesus macaque and green monkey. CAP-Mac is neuron biased in infant Old World primates, exhibits broad tropism in adult rhesus macaques and is vasculature biased in adult marmosets. We demonstrate applications of a single, intravenous dose of CAP-Mac to deliver functional GCaMP for ex vivo calcium imaging across multiple brain areas, or a cocktail of fluorescent reporters for Brainbow-like labelling throughout the macaque brain, circumventing the need for germline manipulations in Old World primates. As such, CAP-Mac is shown to have potential for non-invasive systemic gene transfer in the brains of non-human primates. Crossing the blood-brain barrier in primates is a major obstacle to gene delivery in the brain. Here an adeno-associated virus variant (AAV.CAP-Mac) is identified and demonstrated for crossing the blood-brain barrier and delivering gene sequences to the brain of different non-human primates species.

引用

页码：1241 / +

页数：27

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