USA flag logo/image

An Official Website of the United States Government

Novel Reprogrammed Cells for Differentiation into Cardiomyocytes

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
96378
Program Year/Program:
2010 / SBIR
Agency Tracking Number:
HL104977
Solicitation Year:
N/A
Solicitation Topic Code:
NHLBI
Solicitation Number:
N/A
Small Business Information
NUPOTENTIAL, INC.
340 East Parker Street BATON ROUGE, LA -
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2010
Title: Novel Reprogrammed Cells for Differentiation into Cardiomyocytes
Agency: HHS
Contract: 1R43HL104977-01
Award Amount: $499,765.00
 

Abstract:

DESCRIPTION (provided by applicant): NuPotential will use SBIR funds to improve a patent pending method to reprogram cells using a novel small molecule library. Reprogrammed cells generated using this improved method will be referred to as NuPiPSsm cell s. In addition, NuPotential will partner with VistaGen, Inc., to differentiate NuPiPSsm cells into cardiomyocytes and assess cardiomyocyte functionality. This proposal meets several objectives as outlined in PA-09-249 including: 1) the development of ce ll-based therapies and production of isogenic compatible cells for transplant; 2) evaluation of a potentially safer reprogrammed cell type (referred to as NuPiPSsm cells); 3) assessing whether current ES optimized procedures for developing ES-derived ca rdiac cells can be applied to NuPiPS and NuPiPSsm cells (Current methods developed at VistaGene produce cultures of more than 50% cardiomyocytes and provide a good basis of transplantation cells at various stages of cardiac development.). The reprogra mmed cell lines, differentiated cardiomyocytes and the protein microarrays generated from these SBIR funds will also be made commercially available for applications such as drug discovery and toxicity screening. Direct reprogramming of somatic cells to induced pluripotent stem (iPS) cells has been demonstrated by forced expression of four transcription factors (also referred to as iPS factors). These initial demonstrations have provided valuable insight into molecular mechanisms of somatic cell reprog ramming and raised the possibility that alternative strategies could be developed on an industrial scale to produce pluripotent stem cells without using embryos. However, key challenges remain for reprogramming-based technologies to fully realize commer cial potential. These include improving efficiencies and alleviating the dependence of viral vector transduction for the therapeutic applications of human regenerative medicine. Emerging information has indicated that activation of the endogenous somatic cell reprogramming factor transcription network is a path that addresses both issues. Consistent with results from other labs, NuPotential's preliminary data demonstrate that the endogenous somatic cell reprogramming factor network is active in plurip otent stem cells, but not active in human dermal fibroblasts. Differences between these cell types include pluripotent gene promoter methylation levels and histone modifications, including histone acetylation. Furthermore, our preliminary data indicates that reprogramming efficiency is significantly enhanced by introducing a single transcription factor (instead of the previously described four factors) in combination with specific knockdown of one or more epi-genes (e.g., DNMTs, HDACs) encoding repress ive epigenetic regulators in adult human fibroblasts. Therefore, the proposed SBIR studies are designed to build on these findings and establish proof of principle that novel small molecules, designed and developed by NuPotential, Inc., can replace the l entiviral delivered shRNA component currently required to reprogram human dermal somatic cells to a pluripotent state and that the newly reprogrammed cells (referred to as NuPiPSsm cells) are similar to human ES cells in their differentiation capacity and are sufficiently scalable for industrial applications. To demonstrate this differentiation potential, NuPotential will partner with VistaGen Therapeutics, Inc., one of the leaders in developing and providing stem cell-based systems for drug discovery and development, to compare differentiation in vitro of NuPiPS (NuPotential's original reprogrammed cell type), NuPiPSsm , iPS and human ES cells into a variety of lineages, with a specific focus on cardiomyocytes. Current pluripotent transcription fa ctor-induced somatic cell reprogramming technology (iPS technology) is associated with epigenetic modification of the promoter regions of pluripotent genes. NuPotential's proprietary somatic cell reprogramming platform is based on targeting the epigenome by inhibiting repressive regulatory components (e.g., DNMTs, HDACs) to induce pluripotency genes and restore differentiation potential. NuPotential has filed patents on numerous embodiments of these approaches and has recently been issued its foundatio n patent. To our knowledge this is the first issued patent claiming production of reprogrammed cells without using embryos or transgenes. Fulfillment of the Phase I aims will yield novel information about basic reprogramming mechanisms that will be appli ed to improving the efficiency of nuclear reprogramming by directly inhibiting specific repressive epigenetic regulatory components. In Phase II, NuPotential will use small molecules (derived from a proprietary library designed to contain novel and highl y specific epi-drugs) to specifically inhibit repressive epigenetic regulatory targets identified and validated in Phase I to de-repress pluripotency gene expression and restore a pluripotent state to differentiated somatic cells in culture. Proven effi cient, these small molecules can be used to improve livestock cloning, as well as to produce new reprogrammed pluripotent stem cells (RePSCs ) for therapeutic applications without the use of transgenes, viral vectors, eggs, or embryos. PUBLIC HEAL TH RELEVANCE: NuPotential will use SBIR funds to improve a patent pending method to reprogram cells using a novel small molecule library. Reprogrammed cells generated using this improved method will be referred to as as NuPiPSsm cells. In addition, NuPo tential will partner VistaGen, Inc. to differentiate NuPiPSsm cells into cardiomyocytes and assess cardiomyocyte functionality. This proposal meets several objectives as outlined in PA-09-249 including: 1) the development of cell-based therapies and pr oduction of isogenic compatible cells for transplant; 2) evaluation of a potentially safer reprogrammed cell type (referred to as NuPiPSsm cells); 3) assessing whether current ES optimized procedures for developing ES-derived cardiac cells can be appli ed to NuPiPS and NuPiPSsm cells (Current methods developed at VistaGene produce cultures of more than 50% cardiomyocytes and provide a good basis of transplantation cells at various stages of cardiac development.). The reprogrammed cell lines, differen tiated cardiomyocytes and the protein microarrays generated from these SBIR funds will be made commercially available for applications such as drug discovery and toxicity screening.

Principal Investigator:

Jong S. Rim
2256158956
JSRNUPOTENTIAL@COX.NET

Business Contact:

Rachel Power
kjenupotential@laetc.com
Small Business Information at Submission:

NUPOTENTIAL, INC.
NUPOTENTIAL, INC. 340 East Parker Street BATON ROUGE, LA -

EIN/Tax ID: 126133749
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No