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Tuesday, 10/21/2014 11:23:15 PM

Tuesday, October 21, 2014 11:23:15 PM

Post# of 2204
Regarding TT-034

"...A common observation in clinical and preclinical studies is that pre-existing low levels of NAbs profoundly impact gene transfer efficiency. A recent mechanistic study demonstrated that AAV8 capsid-specific NAb diminished liver deposition of genomes and increased genome distribution to the spleen.26,27 Three separate studies have established the prevalence of NAbs to AAV8 and other serotypes in the human population. The NAb prevalence for AAV8 was noted to be lowest amongst other serotypes in case of pediatric hemophilia patients (22.6%),28 healthy human subjects (19%)29 and a worldwide epidemiology study.30 Despite this relatively favorable antigenic profile for AAV8 in humans, development of strategies to evade NAbs would make a diverse patient cohort eligible for enrollment in clinical trials. Within this framework, generating Nab-escape AAV8 variants and reengineering antigenic domains on the AAV8 capsid31 are likely to yield next generation vector candidates for liver gene transfer. Furthermore, the availability of the AAV8 crystal structure32 should facilitate engineering new lab-derived AAV strains...."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321598/

Good luck and GOD bless,

George
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