AAV-8 is more efficient than AAV-9 in transducing neonatal dog heart

Human Gene Therapy Methods
Xiufang PanDongsheng Duan

Abstract

Adeno-associated virus serotype-8 and 9 (AAV-8 and 9) are the leading candidate vectors to test bodywide neonatal muscle gene therapy in large mammals. We have previously shown that systemic injection of 2-2.5×10(14) viral genome (vg) particles/kg of AAV-9 resulted in widespread skeletal muscle gene transfer in newborn dogs. However, nominal transduction was observed in the heart. In contrast, robust expression was achieved in both skeletal muscle and heart in neonatal dogs with 7.14-9.06×10(14) vg particles/kg of AAV-8. To determine whether superior cardiac transduction of AAV-8 is because of the higher vector dose, we delivered 6.14×10(14) and 9.65×10(14) vg particles/kg of AAV-9 to newborn puppies via the jugular vein. Transduction was examined 2.5 months later. Consistent with our previous reports, we observed robust bodywide transduction in skeletal muscle. However, increased AAV dose only moderately improved heart transduction. It never reached the level achieved by AAV-8. Our results suggest that differential cardiac transduction by AAV-8 and AAV-9 is likely because of the intrinsic property of the viral capsid rather than the vector dose.

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Citations

Jun 25, 2016·Expert Opinion on Orphan Drugs·Yongping YueDongsheng Duan
Aug 12, 2015·Current Opinion in Neurology·Katrin Hollinger, Jeffrey S Chamberlain
Jul 28, 2016·Current Opinion in Virology·Dongsheng Duan
Apr 12, 2017·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Michael E NanceDongsheng Duan
Jul 21, 2017·Human Gene Therapy. Clinical Development·Michael G KatzCharles R Bridges
May 3, 2018·Physiological Reviews·Yu ZhangEric N Olson
Nov 2, 2019·Future Medicinal Chemistry·Ravindra N Singh
Dec 6, 2019·Rheumatology International·George S MetsiosUNKNOWN IMPACT-RMD Consortium
Jan 12, 2021·Molecular Therapy. Methods & Clinical Development·Hiromi Hayashita-KinohTakashi Okada

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Methods Mentioned

BETA
genotyping
transfection
PCR
Assay

Clinical Trials Mentioned

NCT02122952

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