Proceedings of the National Academy of Sciences of the United States of America 106, 16363-16368 (2009) T.
SELECT RESTRICTION ENZYME SITES MACVECTOR TRIAL
Flotte, Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Additionally, several Phase 1 and Phase 2 clinical trials using AAV serotypes 1, 2 and/or chimeric 2.5 have been reported for the treatment of cystic fibrosis, hemophilia, Canavan's disease, Duchenne muscular dystrophy (DMD) and alpha-1 antitrypsin deficiency (M. Recent data from humans showed that targeting the liver with an AAV vector achieves long-term expression of the FIX transgene at therapeutic levels. Both vectors worked efficiently and, in the case of AAV8, long-term expression of the therapeutic transgene was documented. Of the AAV serotypes isolated so far, AAV2 and AAV8 have been used to target the liver of humans affected by severe hemophilia B.
AAV vectors small, non-enveloped, non-pathogenic, helper virus dependent ssDNA virus, and they have numerous serotypes with varying tissue tropisms and transduction efficiencies. At present, adeno-associated virus (AAV) vectors are recognized as the gene transfer vectors of choice for therapeutic applications since they have the best safety (replication deficient, low integration rate and minimum immune response) and efficacy profile for the delivery of genes in vivo. Genetic disorders caused by absence of or a defect in a desirable gene (loss of function) or expression of an undesirable or defective gene (gain of function) lead to a variety of diseases. This invention incorporated by reference the Sequence Listing text copy submitted herewith, which was created on Jun. REFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAM, LISTING APPENDIX SUBMITTED ON A COMPACT DISK The present invention relates to variant AAV capsid polypeptides, wherein the variant AAV capsid polypeptides exhibit increased transduction and/or tropism in human pancreatic tissue or human islets as compared to non-variant parent capsid polypeptides. Government has certain rights in the invention. Government support under Grant Number U01DK089569.
STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 12, 2018, both of which are hereby incorporated by reference in their entireties.
0 kommentar(er)
