Journal article
Adeno-Associated Virus-Based Gene Therapy for Lifelong Correction of Genetic Disease
Human gene therapy, Vol.31(17-18), pp.985-995
09/01/2020
DOI: 10.1089/hum.2020.138
PMCID: PMC7495917
PMID: 32718227
Abstract
The list of successful gene therapy trials using adeno-associated virus (AAV)-based vectors continues to grow and includes a wide range of monogenic diseases. Replication incompetent AAV genomes typically remain episomal and expression dilutes as cells divide and die. Consequently, long-term transgene expression from AAV is best suited for quiescent cell types, such as retinal cells, myocytes, or neurons. For genetic diseases that involve cells with steady turnover, AAV-conferred correction may require routine readministration, where every dose carries the risk of developing an adaptive immune response that renders treatment ineffective. Here, we discuss innovative approaches to permanently modify the host genome using AAV-based platforms, thus potentially requiring only a single dose. Such approaches include using AAV delivery of DNA transposons, homologous recombination templates into safe harbors, and nucleases for targeting integration. In tissues with continual cell turnover, genetic modification of progenitor cell populations will help ensure persistent therapeutic outcomes. Combining the safety profile of AAV-based gene therapy vectors with the ability to integrate a therapeutic transgene creates novel solutions to the challenge of lifelong curative treatments for human genetic diseases.
Details
- Title: Subtitle
- Adeno-Associated Virus-Based Gene Therapy for Lifelong Correction of Genetic Disease
- Creators
- Christian M. Brommel - University of IowaAshley L. Cooney - University of IowaPatrick L. Sinn - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Human gene therapy, Vol.31(17-18), pp.985-995
- Publisher
- Mary Ann Liebert, Inc
- DOI
- 10.1089/hum.2020.138
- PMID
- 32718227
- PMCID
- PMC7495917
- ISSN
- 1043-0342
- eISSN
- 1557-7422
- Number of pages
- 11
- Grant note
- P30 DK-054759 / Center for Gene Therapy of Cystic Fibrosis [NIH] P01 HL-51670; R01 HL-133089 / National Institutes of Health [NIH]; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA SINN19XX0; COONEY18F0 / Cystic Fibrosis Foundation; Italian Cystic Fibrosis Research Foundation
- Language
- English
- Date published
- 09/01/2020
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984297433502771
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