Evolving AAV-delivered therapeutics towards ultimate cures.
J Mol Med (Berl)
; 99(5): 593-617, 2021 05.
Article
in En
| MEDLINE
| ID: mdl-33594520
ABSTRACT
Gene therapy has entered a new era after decades-long efforts, where the recombinant adeno-associated virus (AAV) has stood out as the most potent vector for in vivo gene transfer and demonstrated excellent efficacy and safety profiles in numerous preclinical and clinical studies. Since the first AAV-derived therapeutics Glybera was approved by the European Medicines Agency (EMA) in 2012, there is an increasing number of AAV-based gene augmentation therapies that have been developed and tested for treating incurable genetic diseases. In the subsequent years, the United States Food and Drug Administration (FDA) approved two additional AAV gene therapy products, Luxturna and Zolgensma, to be launched into the market. Recent breakthroughs in genome editing tools and the combined use with AAV vectors have introduced new therapeutic modalities using somatic gene editing strategies. The promising outcomes from preclinical studies have prompted the continuous evolution of AAV-delivered therapeutics and broadened the scope of treatment options for untreatable diseases. Here, we describe the clinical updates of AAV gene therapies and the latest development using AAV to deliver the CRISPR components as gene editing therapeutics. We also discuss the major challenges and safety concerns associated with AAV delivery and CRISPR therapeutics, and highlight the recent achievement and toxicity issues reported from clinical applications.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Therapy
/
Dependovirus
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Gene Editing
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Genetic Vectors
Limits:
Animals
/
Humans
Language:
En
Journal:
J Mol Med (Berl)
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Year:
2021
Document type:
Article
Affiliation country:
China