RETROTHERAPY, LLC — Department of Health and Human Services SBIR Phase I: 102

Description

DESCRIPTION provided by applicant Recent studies by my laboratory and collaborators and by others have demonstrated that RNA trans splicing can correct mutations in many different genes in a wide range of disease model systems including Huntingtonandapos s disease Trans splicing is one of a handful of techniques that can convert the expression of a dominant negative mutation into the normal protein thus simultaneously reducing the cause of the disease and increasing the amount of a necessary protein Trans splicing is the only method that can achieve these results without the requirement for cell division We intend to develop optimal RNA trans splicing molecules RTMs to repair the CAG triplet repeat expansion in exon of the huntingtin gene which is the cause of Huntingtonandapos s disease Huntingtin targeted RTMs will be evaluated for their ability to efficiently and specifically trans splice and replace huntigtin exon at the RNA level by RT PCR at the protein level by Western blot and for their ability to minimize cellular toxicity in differentiated Huntingtonandapos s disease patient iPSC derived striatal neurons by nuclear condensation CellTiter Glo Cell Viability assay TUNEL assay and time lapse microscopy pre clinical candidate RTMs will be identified that most efficiently correct the expression of HTT with minimal toxicity for further development PUBLIC HEALTH RELEVANCE We intend to identify optimal therapeutic candidates to correct the causative mutation of Huntingtonandapos s disease by RNA trans splicing This could lead to the development of a treatment for patients with Huntingtonandapos s disease and ultimately for other genetic disorders