Publication: Distinct transduction of muscle tissue in mice after systemic delivery of AAVpo1 vectors
Issued Date
2019-01-01
Resource Type
ISSN
14765462
09697128
09697128
Other identifier(s)
2-s2.0-85074042381
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Gene Therapy. (2019)
Suggested Citation
Warut Tulalamba, Jonas Weinmann, Quang Hong Pham, Jihad El Andari, Thierry VandenDriessche, Marinee K. Chuah, Dirk Grimm Distinct transduction of muscle tissue in mice after systemic delivery of AAVpo1 vectors. Gene Therapy. (2019). doi:10.1038/s41434-019-0106-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/50403
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Distinct transduction of muscle tissue in mice after systemic delivery of AAVpo1 vectors
Abstract
© 2019, Springer Nature Limited. The human musculature is a promising and pivotal target for human gene therapy, owing to numerous diseases that affect this tissue and that are often monogenic, making them amenable to treatment and potentially cure on the genetic level. Particularly attractive would be the possibility to deliver clinically relevant DNA to muscle tissue from a minimally invasive, intravenous vector delivery. To date, this aim has been approximated by the use of Adeno-associated viruses (AAV) of different serotypes (rh.74, 8, 9) that are effective, but unfortunately not specific to the muscle and hence not ideal for use in patients. Here, we have thus studied the muscle tropism and activity of another AAV serotype, AAVpo1, that was previously isolated from pigs and found to efficiently transduce muscle following direct intramuscular injection in mice. The new data reported here substantiate the usefulness of AAVpo1 for muscle gene therapies by showing, for the first time, its ability to robustly transduce all major muscle tissues, including heart and diaphragm, from peripheral infusion. Importantly, in stark contrast to AAV9 that forms the basis for ongoing clinical gene therapy trials in the muscle, AAVpo1 is nearly completely detargeted from the liver, making it a very attractive and potentially safer option.