Chemical approaches to probe and engineer AAV vectors

Area of Science:

• Biotechnology
• Molecular Biology
• Gene Therapy

Background:

• Adeno-associated virus (AAV) is a leading vector for *in vivo* gene therapy due to its safety and efficacy.
• Wild-type AAV capsids face limitations like poor tissue specificity, high dosage requirements, and pre-existing immunity.
• Engineering AAV capsids is crucial for improving therapeutic outcomes and safety.

Purpose of the Study:

• To review recent advancements in AAV capsid engineering.
• To highlight chemical modification as a powerful strategy for AAV capsid engineering.
• To discuss the potential of engineered AAV capsids for next-generation gene therapies.

Main Methods:

• Focus on chemical modification strategies for AAV capsid engineering.
• Discuss late-stage modification of assembled capsids.
• Consider modifications at natural and noncanonical amino acid residues.

Main Results:

• Chemical modification provides a versatile approach to engineer AAV capsid properties.
• This method can overcome limitations of wild-type AAV capsids, such as tissue specificity and immunogenicity.
• Engineered capsids hold promise for improved AAV-based gene therapies.

Conclusions:

• Chemical modification of AAV capsids is a key strategy for advancing gene therapy.
• Engineered AAV capsids can enhance therapeutic efficacy and safety.
• This approach is vital for realizing the full potential of AAV gene therapy.