Preclinical Hemophilia Gene Therapy Study with Non-human Primates

点击翻译按钮获取中文摘要

The Hemophilia gene therapy study was carried out according to the research plan. We have completed the FIX gene expression study with adeno-associated virus (AAV) vectors in mice for hemophilia B gene therapy and the hemophilia B gene therapy preclinical study is currently conducted with macaques. The AAV8 vector carrying the macaque FIX T262A was effective to express macaque FIX T262A to the therapeutic level in anti-AAV8 antibody-negative macaques whereas the vector was unable to express macaque FIX T262A to the therapeutic level in anti-AAV8 antibody-positive macaques. The novel vector-injection method for evading the inhibitory effect of anti-AAV8 antibody was developed and was effective to express the transgene-derived macaque FIX T262A in anti-AAV8 antibody-positive macaques. Human FVIII could be expressed with the AAV8 vector to the therapeutic level in FVIII deficient mice. A novel hemophilia A model animal (cloned hemophilia A pig) was generated by nuclear transfer cloning. The efficient and site specific integration of FVIII gene into the chromosome 19 was achieved with the AAV2 Rep gene. New monoclonal antibodies raised against B domain-deleted human FVIII were developed and used to quantify B domain deleted human FVIII specifically.