Development of a novel biologic medical product for Dyskeratosis Congenita

Period of Performance: 08/05/2016 - 01/31/2017


Phase 1 SBIR

Recipient Firm

Elixirgen, LLC
Principal Investigator
Principal Investigator


Program Director/Principal Investigator (Last, First, Middle): Ko, Minoru, S.H.Dyskeratosis congenita (DKC) is a rare genetic disease that occurs at the rate of 1 in 1 million births and causedby mutations in genes involved in the regulation of telomere lengths. Although there are multiple genemutations causing DKC, all the patients carry significantly shorter telomeres and eventually develop bonemarrow failure, which is the main cause of premature mortality in DKC patients. There has been no effectivetreatment for DKC patients. Here, we would like to propose the product of human ZSCAN4 gene as a biologicto treat DKC patients. We have originally identified mouse Zscan4, a novel protein expressed specifically in 2-cell stage mouse embryos, and have published a number of unusual features of Zscan4 functions in mouse EScells: (i) to rapidly extend telomeres by homologous recombination (called alternative lengthening oftelomeres), which is independent of telomerase (ii) to increase genome stability and maintain normal karyotypeby transient and occasional expression, (iii) to increase developmental potential, (iv) to block de novo synthesisof proteins transiently, (v) to increase the efficiency and quality of induced pluripotent stem (iPS) cells, whenused as one of the reprogramming factors, and (vi) to function as a potent epigenetic modifier and transientlyopen chromatin. Based on these functions of mouse Zscan4, we hypothesize that transient overexpression ofhuman ZSCAN4 protein extends telomeres in bone marrow cells from DKC patients by homologousrecombination-based mechanisms and eventually alleviates bone marrow failure in DKC patients. In this SBIRPhase I proposal, we would like to demonstrate that transient overexpression of ZSCAN4 elongates telomeres infibroblast cells derived from DKC patients. We would also like to demonstrate that ZSCAN4 biologics can bedelivered to bone marrow using a mouse model. The proposed project, if successful, will offer a first steptowards a dramatically new therapy for patients with DKC. In addition, the biologic's mechanisms are verymuch applicable to other related bone marrow and telomere related disorders, such as myelodysplasticsyndrome and Fanconi anemia.OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page