Adeno-Associated Virus Vector for Central Nervous System Gene Therapy

Danqing Zhu; Adam J Schieferecke; Paola A Lopez; David V Schaffer

doi:10.1016/j.molmed.2021.03.010

Adeno-Associated Virus Vector for Central Nervous System Gene Therapy

Trends Mol Med. 2021 Jun;27(6):524-537. doi: 10.1016/j.molmed.2021.03.010. Epub 2021 Apr 21.

Authors

Danqing Zhu¹, Adam J Schieferecke², Paola A Lopez³, David V Schaffer⁴

Affiliations

¹ California Institute for Quantitative Biosciences, University of California, Berkeley, CA, 94720, USA.
² Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA.
³ Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.
⁴ California Institute for Quantitative Biosciences, University of California, Berkeley, CA, 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA; Department of Bioengineering, University of California, Berkeley, CA, 94720, USA; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, CA, 94720, USA. Electronic address: schaffer@berkeley.edu.

PMID: 33895085
DOI: 10.1016/j.molmed.2021.03.010

Abstract

The past several years have witnessed significant advances in the development of therapeutic gene delivery for neurological disorders of the central nervous system (CNS). In particular, genome-wide sequencing analysis has deepened our understanding of mutations that underlie many monogenic disorders, which in turn has contributed to clinical advances involving adeno-associated virus (AAV) vector delivery of replacement genes to treat recessive disorders. Moreover, gene therapy has been further bolstered with advances in genome editing tools that allow researchers to silence, repair, and amend endogenous genes. However, despite strong preclinical and clinical progress, challenges remain, including delivery and safety. Here, we discuss advances in AAV engineering, recent developments in cargo design, and translation of these technologies towards clinical progress.

Keywords: AAV; CNS; gene therapy.

Publication types

Review

MeSH terms

Animals
Central Nervous System Diseases / genetics
Central Nervous System Diseases / therapy*
Dependovirus / genetics*
Genetic Therapy / methods*
Genetic Vectors / administration & dosage*
Genetic Vectors / genetics
Humans
Phenotype