The objective of this contract is to develop chemically modified mimics of microRNAs with improved activity and stability for the treatment of many diseases

Approximatelymillion people are currently living with human immunodeficiency virusHIVinfection worldwideWith no curative therapy on the horizonpatients must be on antiretroviral therapyARTfor decades to manage their diseaseBecause ART targets only actively replicating virustreatment interruption or ART failure leads to rebound of latent virusRNA therapeutics have shown great promise as a new mechanism for treating HIVhoweverdelivery to target cells at therapeutic doses remains a clinical problemmiRecule Incproposes to develop a mimic of the anti HIV microRNA miRpmiRecule drug candidate MCencapsulated in a dendrimer that specifically targets HIV co receptor CXCRBinding of MCdendriplex to CXCRinduces receptor mediated endocytosis delivering our therapeutic microRNA mimic to the cytosol of targeted cellsSince MCsimultaneously targets several key regulators of the HIV lifecycle including viral transcriptwe predict that it will be less susceptible to the development of resistance and enable ablock and lockeradication strategy by preventing latent HIVfrom rebounding following treatment interruptionsCompletion of this phasecontract will identify a vastly durable mimic of miRp using proprietary combinations of nucleic acid modificationsdemonstrate effective delivery to CXCRlymphocytes in vivovalidate miRp mimic inblock and lockmodelsand assess potential non target toxicitiesIn phase II we will improve formulationsestablish CMC processes to support synthesize up to Phaseclinical trialsand begin IND enabling studiesi ePKADMEpivotal toxicityetcand dose range finding experiments