Efficient and durable gene transfer to transplanted heart using adeno-associated virus 9 vector

Area of Science:

• Cardiovascular Research
• Gene Therapy
• Viral Vector Technology

Background:

• Investigating the efficacy and durability of gene transfer to transplanted hearts.
• Focusing on recombinant adeno-associated virus serotype 9 (rAAV9) vectors.

Purpose of the Study:

• To assess rAAV9 vector-mediated gene transfer to transplanted rat hearts.
• To evaluate the durability of gene transfer over time.

Main Methods:

• Ex vivo perfusion of rat hearts with rAAV9-CMV-lacZ vector prior to transplantation.
• Dose-ranging studies (2 x 10^9 to 2 x 10^12 viral genomes/ml).
• Assessment of lacZ expression at 10 days and 3 months post-transplantation using histology, ELISA, and RT-PCR.

Main Results:

• Gene transfer efficiency correlated positively with vector dose (p < 0.0001).
• Myocardial transduction reached up to 71.74% at the highest dose.
• Cardiac gene expression remained consistent at both 10 days and 3 months, with no off-target organ transduction.

Conclusions:

• rAAV9 enables efficient and durable gene transfer to transplanted hearts via ex vivo perfusion.
• AAV9 represents a promising vector for developing cardiac gene therapies.