Adenine Base Editing for Autologous Hematopoietic Stem Cell Gene Therapy of CD3δ SCID
Grant Award Details
Grant Type:
Grant Number:
TRAN1-15257
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$5,966,928
Status:
Active
Grant Application Details
Application Title:
Adenine Base Editing for Autologous Hematopoietic Stem Cell Gene Therapy of CD3δ SCID
Public Abstract:
Translational Candidate
The translational candidate is Autologous Hematopoietic Stem and Progenitor Cells from CD3δ SCID Patients Corrected by Adenine Base Editing
Area of Impact
The candidate will provide treatment for a fatal inborn error of immunity (CD3δ SCID) affecting a genetically-isolated population.
Mechanism of Action
Autologous Hematopoietic Stem and Progenitor cells from CD3δ SCID Patients Corrected by Adenine Base Editing have the biological activity of hematopoietic stem cells (HSC) to achieve long-term engraftment after autologous transplantation. The correction of the pathogenic CD3D mutation allows the HSC to support normal T lymphopoiesis to reverse the life-threatening SCID.
Unmet Medical Need
By avoiding the immune complications of allogeneic hematopoietic stem cell transplantation (HSCT), autologous transplant of corrected cells should be safer: no need of a matched donor, reduced risk of treatment-related toxicity using reduced intensity conditioning, and no risk of GvHD.
Project Objective
Pre-IND meeting for guidance on IND advance
Major Proposed Activities
The translational candidate is Autologous Hematopoietic Stem and Progenitor Cells from CD3δ SCID Patients Corrected by Adenine Base Editing
Area of Impact
The candidate will provide treatment for a fatal inborn error of immunity (CD3δ SCID) affecting a genetically-isolated population.
Mechanism of Action
Autologous Hematopoietic Stem and Progenitor cells from CD3δ SCID Patients Corrected by Adenine Base Editing have the biological activity of hematopoietic stem cells (HSC) to achieve long-term engraftment after autologous transplantation. The correction of the pathogenic CD3D mutation allows the HSC to support normal T lymphopoiesis to reverse the life-threatening SCID.
Unmet Medical Need
By avoiding the immune complications of allogeneic hematopoietic stem cell transplantation (HSCT), autologous transplant of corrected cells should be safer: no need of a matched donor, reduced risk of treatment-related toxicity using reduced intensity conditioning, and no risk of GvHD.
Project Objective
Pre-IND meeting for guidance on IND advance
Major Proposed Activities
- Develop Manufacturing Plan; Produce a Clinical-Scale Lot(s) of Drug Product
- Perform Additional Pharmacology and Toxicology Studies
- Prepare Briefing Package and Conduct Pre-IND Meeting with the FDA
Statement of Benefit to California:
Since initiation of newborn screening for SCID in California, 1 of 65,000 births (~8/year) has been diagnosed. All SCID patients require hematopoietic stem cell transplantation (HSCT). Autologous HSCT by gene therapy may be effective and safer than allogenic HSCT. Optimization and implementation of novel methods such as base editing may extend this approach to many blood cell diseases that require HSCT in California (as Sickle Cell Disease) providing more beneficial and cost-effective therapies.