Grant Award Details

Genome Editing of Sinusoidal Endothelial Stem Cells for Permanent Correction of Hemophilia A
Grant Type: 
Grant Number: 
DISC2-10524
Project Objective: 

  • To develop an AAVHSC- mediated homologous recombination approach for in vivo correction of the Factor VIII gene in sinusoidal endothelial stem cells (SESC), for treating Hemophilia A caused by I22 inversion

Investigator: 
Disease Focus: 
Blood Disorders
Hemophilia A
Human Stem Cell Use: 
Adult Stem Cell
Award Value: 
$2,182,193
Status: 
Active

Progress Reports

Reporting Period: 
Year 2

Grant Application Details

Application Title: 
  • Genome Editing of Sinusoidal Endothelial Stem Cells for Permanent Correction of Hemophilia A
Public Abstract: 

Research Objective

Therapeutic candidate to cure hemophilia A is AAV-based genome editing vector that corrects the disease-causing mutation in the factor VIII gene in patient stem cells to develop a permanent cure.

Impact

Permanent correction of hemophilia A by editing mutations in the FVIII gene in stem cells.
Develop a precise and efficient non-nuclease genome editing technology for editing somatic stem cells in vivo.

Major Proposed Activities

  • Identification of optimal genome editing vector for editing the FVIII gene in human endothelial cells, somatic stem cells and immortalized cells derived from hemophilia A patient.
  • Test successful in vitro genome editing in the human stem cells that give rise to the clotting factor VIII producing cells.
  • Demonstrate genome editing of the FVIII gene in human stem cells and their progeny, to provide proof of concept of the gene editing strategy for therapeutic correction of the mutation.
  • To identify the best genome editing vector for correcting xenotransplanted human stem cells in immune-deficient mice in vivo.
  • Functional evidence of genome editing of FVIII gene in regenerating mouse liver after partial hepatectomy.
  • Test therapeutic correction of hemophilia A in a dog model to obtain proof of efficacy of this genome editing strategy. This information will facilitate translation and discussions with the FDA.
Statement of Benefit to California: 

Hemophilia A is an incurable, devastating inherited bleeding disorder caused by the lack of functional clotting factor Vlll. The management of hemophilia A poses a large economic and quality of life burden. Twenty percent of all hemophilia patients live in California. We plan to develop a therapeutic candidate for the correction of the causative factor VIII mutations in stem cells using genome editing in order to develop a permanent cure for hemophilia A.

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