A versatile viral toolkit for functional discovery in the nervous system.


Journal

Cell reports methods
ISSN: 2667-2375
Titre abrégé: Cell Rep Methods
Pays: United States
ID NLM: 9918227360606676

Informations de publication

Date de publication:
20 06 2022
Historique:
received: 07 12 2021
revised: 21 03 2022
accepted: 04 05 2022
entrez: 5 7 2022
pubmed: 6 7 2022
medline: 6 7 2022
Statut: epublish

Résumé

The ability to precisely control transgene expression is essential for basic research and clinical applications. Adeno-associated viruses (AAVs) are non-pathogenic and can be used to drive stable expression in virtually any tissue, cell type, or species, but their limited genomic payload results in a trade-off between the transgenes that can be incorporated and the complexity of the regulatory elements controlling their expression. Resolving these competing imperatives in complex experiments inevitably results in compromises. Here, we assemble an optimized viral toolkit (VTK) that addresses these limitations and allows for efficient combinatorial targeting of cell types. Moreover, their modular design explicitly enables further refinements. We achieve this in compact vectors by integrating structural improvements of AAV vectors with innovative molecular tools. We illustrate the potential of this approach through a systematic demonstration of their utility for targeting cell types and querying their biology using a wide array of genetically encoded tools.

Identifiants

pubmed: 35784651
doi: 10.1016/j.crmeth.2022.100225
pii: S2667-2375(22)00088-1
pmc: PMC9243523
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Pagination

100225

Subventions

Organisme : NIMH NIH HHS
ID : R01 MH111529
Pays : United States
Organisme : NIMH NIH HHS
ID : UG3 MH120096
Pays : United States

Informations de copyright

© 2022 The Author(s).

Déclaration de conflit d'intérêts

J.D. is founder, shareholder, and employee of Regel Therapeutics. G.F. is founder and shareholder of Regel Therapeutics. The work presented in this manuscript is unrelated to any aspect of Regel Therapeutics’ focus, work, or interest.

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Auteurs

Gabrielle Pouchelon (G)

Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.
Harvard Medical School, Blavatnik Institute, Neurobiology, Boston, MA 02115, USA.

Josselyn Vergara (J)

Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.

Justin McMahon (J)

Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.

Bram L Gorissen (BL)

Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.
Harvard Medical School, Blavatnik Institute, Neurobiology, Boston, MA 02115, USA.

Jessica D Lin (JD)

Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.

Douglas Vormstein-Schneider (D)

Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.

Jason L Niehaus (JL)

Addgene, Watertown, MA 02472, USA.

Timothy J Burbridge (TJ)

Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.
Harvard Medical School, Blavatnik Institute, Neurobiology, Boston, MA 02115, USA.

Jason C Wester (JC)

Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.

Mia Sherer (M)

Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.
Harvard Medical School, Blavatnik Institute, Neurobiology, Boston, MA 02115, USA.

Marian Fernandez-Otero (M)

Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.
Harvard Medical School, Blavatnik Institute, Neurobiology, Boston, MA 02115, USA.

Kathryn C Allaway (KC)

Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.
Harvard Medical School, Blavatnik Institute, Neurobiology, Boston, MA 02115, USA.

Kenneth Pelkey (K)

Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.

Ramesh Chittajallu (R)

Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.

Chris J McBain (CJ)

Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.

Melina Fan (M)

Addgene, Watertown, MA 02472, USA.

Jason S Nasse (JS)

Addgene, Watertown, MA 02472, USA.

Gregg A Wildenberg (GA)

Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA.
Biosciences Division, Argonne National Laboratory, Lemont, IL 60439, USA.

Gordon Fishell (G)

Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.
Harvard Medical School, Blavatnik Institute, Neurobiology, Boston, MA 02115, USA.

Jordane Dimidschstein (J)

Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.

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Classifications MeSH