UNIVERSITY OF MASSACHUSETTS
The main goal of the supplemental ARRA funding is to find out the mRNA content of wild type huntingitn and mutant huntingtin (expanded CAG repeats) in human striatum and cortex. This is a critical question in potential therapy for Huntington's disease. There is an improtant difference between gene silencing (both huntingtin alleles) and allele-selective silencing. In gene silencing, both wild type and mutant huntingtin mRNA would be knocked down. In allele specific silencing, the mutant huntingtin allele would be knocked down and the wild type would be preserved. If Huntington's disease striatum and cortex expressed more mutant than wild type huntingtin mRNA, equimolar knock down would lead to accumulation of mutant huntingtin and the disease could get worse.