Method is more efficient and economical compared with other procedures

A method to create a faster and lower cost alternative for a gene therapy tool has been developed by Boston University School of Medicine (BUSM) researchers.

Gene therapy is a clinical technique that introduce genes to treat disease. One approach is to use adeno-associated virus (AAV) as a tool to deliver the gene, but production of large quantities of AAV tends to be complicated and costly.

Now for the first time, BUSM researchers have developed an advanced protocol to produce large quantities of AAVs, viral vectors that can deliver a specific gene into humans and animals.

According to the researchers, AAVs are also powerful research tools when combined with modern gene-editing technologies and can serve as a practical alternative to genetically modified animal models. However, a major drawback has been the time and cost to produce quantities of AAV to be used for animals in the lab. This advanced technique bypasses developmental effects that can arise from conventional gene manipulation in animals, while saving time, reducing the numbers of animals used in research and eventually research cost.

“Our protocol helps to produce AAVs efficiently and economically in regular laboratories so that researchers can easily conduct a pre-clinical trials for gene therapy,” explained co-corresponding author Markus Bachschmid, PhD, assistant professor of medicine at BUSM.

“Several labs in the Boston area and Japan have already tested this new protocol and found it useful,” said co-corresponding author Reiko Matsui, MD, assistant professor of medicine at BUSM. “Our hope is that many laboratories can adapt these procedures to accelerate research and promote gene therapy.”

Gene therapy using AAV is a rapidly emerging field in clinical therapy. The recent release of the FDA approved AAV-based drug Zolgensma for treating spinal muscular atrophy is a landmark in human gene therapy and demonstrates the high potential of AAV.

These findings appear online in Scientific Reports.

This work was supported by NIH grants R01 DK103750, R01 HL133013, and R03 AG 051857, American Heart Association “Grant in Aid” 16GRNT27660006, European Cooperation in Science and Technology (COST Action BM1203/EU-ROS), and the Metabolic Clinical Research Collaborative. This work was also supported by the NIH/Boston University CTSI grant 1UL1TR001430 to M.M.B., and R.M. M.M.B. was also supported by the Evans Junior Faculty Research Award by the Department of Medicine of Boston University. B.F. and A.F. were supported by NIH T32 HL07224 Multidisciplinary Training in Cardiovascular Research through the Whitaker Cardiovascular Institute. T.K. was supported by the National Defense Medical College foreign exchange program. T.K., Y.I., and T.A. were supported by a grant awarded by the Japanese Ministry of Defense, and MEXT/JSPS KAKENHI Grant-in-Aid for Scientific Research (JP 18H02815 and JP 18K8120). The grant from Kilo Diabetes & Vascular Research Foundation supported Y.I. for development of plasmid works. I.L. was supported by the American Heart Association 15FTF25890062.