Clinical gene therapy using recombinant adeno-associated virus vectors

Area of Science:

• Virology
• Gene Therapy
• Biotechnology

Background:

• Recombinant adeno-associated virus (rAAV) vectors are derived from wild-type adeno-associated viruses (AAVs).
• AAVs are ubiquitous in humans and nonhuman primates, with no known associated pathology.
• AAVs have a natural propensity for persistence in human cells, making them suitable for gene therapy.

Purpose of the Study:

• To review the suitability of rAAV vectors for clinical gene therapy.
• To highlight the safety profile and natural history of AAVs.
• To discuss the expansion of AAV vector applications through diverse capsid isolates.

Main Methods:

• Review of AAV biology and natural history.
• Analysis of preclinical studies in various animal models (mice, rabbits, dogs, nonhuman primates).
• Examination of data from over 40 approved clinical trials using AAV vectors.

Main Results:

• Over 40 clinical trials using rAAV vectors have been approved.
• AAV serotype 2 vectors were used in initial trials.
• Current trials employ AAV2 genomes in AAV1 capsids for enhanced muscle gene delivery.
• Over 120 capsid isolates are now available, broadening potential applications.

Conclusions:

• rAAV vectors are well-suited for clinical gene therapy due to their safety and persistence.
• The diversity of AAV capsids significantly expands the potential applications of AAV-based gene therapy.
• Ongoing research and clinical trials continue to advance the use of rAAV vectors for various diseases.