Developing efficient and safe cell-permeable reprogramming peptides for generation of iPS cells.

DESCRIPTION provided by applicant The groundbreaking discovery of induced pluripotent stem cells iPSCs has opened a new page for developing personalized cell based therapies against various devastating human diseases without ethical concerns of using human embryonic stem cells However the future clinical applications of iPSCs remain in doubt due to potential risks of undesired genomic alteration and tumor formation Generation of iPSCs by transient expression of pluripotent factors has decreased the safety concerns yet the reprogramming efficiency remains low In this application we propose to develop an improved cell permeable protein based method to efficiently generate iPSCs We have developed a rational approach to systematically engineer produce and validate robust cell penetrating reprogramming peptides that will overcome the key barriers to achieve high efficiency and safe cellular reprogramming The technology will enable us to efficiently produce patient compatible iPSCs with the best safety profiles so as to derive other cell types safely for transplantation or for other types of clinical applications Two Aims are proposed Specific Aim Months To construct a library of cell permeable human iPSC reprogramming proteins with modifications that would increase their reprogramming efficiency at Vivoscript Inc Specific Aim Months To evaluate the efficiency of these proteins in iPSC generation in Chenandapos s lab at Sanford Burnham Medical Research Institute

PUBLIC HEALTH RELEVANCE We are developing robust cell penetrating peptides to overcome the limitations of current technologies for an efficient generation of human induced pluripotent stem cells iPSCs Our novel technology will enable us to efficiently produce patient compatible iPSCs with the best safety profiles so as to benefit the public by deriving other cell types from these iPSCs for future clinical therapy or drug screens