CRISPR-C2C2 AS A POTENTIAL THERAPY FOR ALZHEIMER'S DISEASE THROUGH SPECIFIC TARGETING AND REDUCTION OF RCAN1.1 MRNA ISOFORM

Abstract

Currently there are no effective treatments or cures for the debilitating and deadly neurodegenerative disease Alzheimer's disease (AD), and therefore there is a need for novel target identification that will lead to effective therapies for this disease. There is strong evidence that overexpression of RCAN1.1 causes AD progression through hyperphosphorylation of the tau protein which causes development of neurofibrillary tangles, eventually leading to neuronal loss via apoptosis. For this reason, RCAN1.1 provides a novel target for silencing therapeutics. On the contrary, expression of RCAN 1.4 has shown a protective effect for neurons and an overall improvement in the clinical symptoms associated with AD. Therefore a novel tool is needed that can specifically target RCAN1.1 mRNA while preserving expression of RCAN 1.4. CRISPR-C2c2 is a novel RNA-guided RNA-targeting system capable of targeting specific RNAs via a programmable crRNA guide. The CRISPR-C2c2 system is the tool that can provide the mechanism for specific targeting of RCAN1.1 mRNA therefore potentially providing vital treatment for Alzheimer's disease.