HEPATX CORPORATION — Department of Health and Human Services SBIR Phase I: 400

Description

Novel cell therapies promise to be highly potent solutions for unmet medical needsincluding liver failurediabetesand other diseasesTo meet the anticipated demandlarge numbers of primary cells will often be neededIn particularmesenchymal stromal cellsMSCsare a promising cell type for therapeutic applicationsIncreased cell yield per donor would significantly impact the ability of cell therapy companies including Hepatx to scale manufacturing and provide a commercially viable therapeutic productHoweverproduction of commercial quantities of MSCs while maintaining therapeutic potency is challengingHuman MSCs lack endogenous telomerase activity and the resultant telomere shortening causes them to senesce and lose functionIntroduction of telomerase reverse transcriptaseTERTto MSCs preserves the growthdifferentiationand immunomodulatory effects and can make MSCs amenable to scaled up manufacturing processesWe will employ a recently developed method of rapidly and transiently extending telomeres by delivery of TERT that has several advantages for telomere extensionit is transientrapidnon immortalizinghypoimmunogenicand safeHere we propose to develop scalableGMP compatible methods for transient introduction of TERT mRNA that will extend telomeres to increase the functional lifespan and therapeutic utility of MSCsHepatx in collaboration with Rejuvenation TechnologiesIncwill develop the processes necessary to extend telomeres in cultured MSCs at sufficient scale to enable development of larger tiered cell banksthen validate that the expanded MSCs maintain their native multilineage differentiation potential and immunosuppressive activityAimDefine optimal conditions for extension of telomeres in a bioreactor settingWe will optimize procedures for transfection of RTI s transient telomere extension formulation into MSCs with high efficiency and viabilityOnce optimal conditions for transfection have been determinedtelomerase activity will be measuredCompatibility with liter scale bioreactor conditions will be verifiedAimCharacterize biological performance of ASC treated with TERT nanoparticles Using the optimized transfection method from Aimwe will deliver TERT mRNA to MSCs and measure their proliferative capacity and verify that the treated MSC retain capacity to differentiate into hepatocytesadipocyteschondrocytesosteoblastsAngiogenic cytokine production will be assayed and immunosuppressive activity will be measuredPilot testing of novel tiered cell banking processes will be performedThis approach can offer greater expansion of ASC for not only Hepatx s MSC derived productbut also for other cell based therapeutic productsIf successfulthese studies will demonstrate that MSC production can be scaled without loss of functionA phase II SBIR will develop GMP compliant methods and extend the results to other cell types Cell therapies promise to deliver highly potent solutions for unmet medical needsHepatx and Rejuvenation TechnologiesIncwill develop methods to scale manufacturing of cell therapies to meet increasing demandThis will enhance commercial viability of these advanced therapies