A Treatment for Artemis-deficient Severe Combined Immunodeficiency using Non-Viral CRISPR-driven Safe Harbor Transgenesis in Hematopoietic Stem Cells
Grant Award Details
Grant Type:
Grant Number:
DISC2-14130
Investigator(s):
Human Stem Cell Use:
Award Value:
$1,809,372
Status:
Active
Grant Application Details
Application Title:
A Treatment for Artemis-deficient Severe Combined Immunodeficiency using Non-Viral CRISPR-driven Safe Harbor Transgenesis in Hematopoietic Stem Cells
Public Abstract:
Research Objective
A Treatment for Artemis-deficient Severe Combined Immunodeficiency using Non-Viral CRISPR-driven Safe Harbor Transgenesis in Hematopoietic Stem Cells
Impact
We aim to develop a novel genome editing based therapy for Artemis-deficient severe combined immunodeficiency that would improve upon prior gene therapies in efficacy, safety, and scalability.
Major Proposed Activities
A Treatment for Artemis-deficient Severe Combined Immunodeficiency using Non-Viral CRISPR-driven Safe Harbor Transgenesis in Hematopoietic Stem Cells
Impact
We aim to develop a novel genome editing based therapy for Artemis-deficient severe combined immunodeficiency that would improve upon prior gene therapies in efficacy, safety, and scalability.
Major Proposed Activities
- Discover optimal approach for nonviral targeted integration of a functional DCLRE1C transgene into AAVS1 genomic safe harbor in hematopoietic stem and progenitor cells (HSPCs)
- Discover optimal approach for generating Artemis-deficient HSPCs and characterize resulting cells
- Demonstrate ex vivo restoration of Artemis function using Artemis-deficient HSPCs
- Demonstrate in vivo restoration of Artemis function using Artemis-deficient HSPCs
Statement of Benefit to California:
Our target disease indication, ART-SCID, carries significant risk of death and long-term comorbidities and disproportionately affects descendants of Navajo and Apache Native Americans, although it can affect individuals of any genetic background. We aim to develop a genome editing therapy in blood stem cells using genome editing that will improve upon prior gene therapies with better efficacy, safety, and scalability, which will improve patient access..
