Clinical gene therapy development for the central nervous system: Candidates and challenges for AAVs

Tiffany W Leong; Arindam Pal; Qi Cai; Zhenghong Gao; Xiaoqing Li; Leonidas Bleris; Heather N Hayenga; Zhenpeng Qin

doi:10.1016/j.jconrel.2023.04.009

Clinical gene therapy development for the central nervous system: Candidates and challenges for AAVs

J Control Release. 2023 May:357:511-530. doi: 10.1016/j.jconrel.2023.04.009. Epub 2023 Apr 21.

Authors

Tiffany W Leong¹, Arindam Pal¹, Qi Cai², Zhenghong Gao², Xiaoqing Li¹, Leonidas Bleris³, Heather N Hayenga¹, Zhenpeng Qin⁴

Affiliations

¹ Department of Bioengineering, The University of Texas at Dallas, Richardson, TX 75080, USA.
² Department of Mechanical Engineering, The University of Texas at Dallas, Richardson, TX 75080, USA.
³ Department of Bioengineering, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Systems Biology, University of Texas at Dallas, Richardson, TX 75080, USA; Department of Biological Sciences, University of Texas at Dallas, Richardson, TX 75080, USA.
⁴ Department of Bioengineering, The University of Texas at Dallas, Richardson, TX 75080, USA; Department of Mechanical Engineering, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080, USA; Department of Surgery, The University of Texas at Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: [email protected].

PMID: 37040842
DOI: 10.1016/j.jconrel.2023.04.009

Abstract

Many diseases affecting the central nervous system (CNS) are deadly but less understood, leading to impaired mental and motor capabilities and poor patient prospects. Gene therapy is a promising therapeutic modality for correcting many genetic disorders, expanding in breadth and scope with further advances. This review summarizes the candidate CNS disorders for gene therapy, mechanisms of gene therapy, and recent clinical advances and limitations of gene therapy in CNS disorders. We highlight that improving delivery across CNS barriers, safety, monitoring techniques, and multiplexing therapies are predominant factors in advancing long-term outcomes from gene therapy.

Keywords: Adeno-associated virus; CNS; Gene therapy.

Publication types

Review
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Central Nervous System
Central Nervous System Diseases* / genetics
Central Nervous System Diseases* / therapy
Genetic Therapy / methods
Genetic Vectors* / genetics
Humans