Gene therapy for familial amyloidotic polyneuropathy (FAP)

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Liver transplantation for familial amyloidotic polyneuropathy (FAP) revealed that replacement of the variant transthyretin (TTR) gene is effective for halting clinical symptoms of FAP. Thus, we need to develop a new treatment that prevents production of the variant TTR in the liver and retina. In this study, we used HepG2 cells to show in vitro conversion of the TTR gene by single-stranded oligonucleotides (SSOs), embedded in atelocollagen, designed to promote endogenous repair of genomic DNA. For the in vivo portion of the study, we used rabbit eyes and liver from transgenic mice whose intrinsic wild-type TTR gene was replaced by the murine TTR Val30Met gene. The rate of gene conversion was determined by real-time RCR combined with mutual-allele-specific amplification. Our results indicate that the rate of gene conversion was approximately 11%, 1%, and 9% of the total TTR gene in HepG2 cells, rabbit eyes, and liver from transgenic mice, respectively. Gene therapy via this method may therefore be a promising alternative to liver transplantation for treatment of FAP.