Evaluation of Gene Therapy Approaches for Autosomal Recessive Hyper IgE Syndrome Due to Mutations in DOCK8
Grant Award Details
Grant Number:
DISC2P-11791
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$234,000
Status:
Closed
Progress Reports
Reporting Period:
Final Full Progress Reporting
Grant Application Details
Application Title:
Evaluation of Gene Therapy Approaches for Autosomal Recessive Hyper IgE Syndrome Due to Mutations in DOCK8
Public Abstract:
Research Objective
We propose to evaluate both gene addition with viral vectors and CRISPR-based gene editing of a patient's own bone marrow stem cells as a curative therapy for autosomal recessive hyper-IgE syndrome.
Impact
Demonstration of effective stem cell gene therapy for a gene as large as DOCK8 opens the door for this approach in many other human diseases due to mutations in similarly large genes.
Major Proposed Activities
["Develop and evaluate a gene addition approach for DOCK8 using lentiviral vectors.", "Develop and evaluate a CRISPR-based targeted gene editing approach to site-specifically correct all defects in DOCK8."]
We propose to evaluate both gene addition with viral vectors and CRISPR-based gene editing of a patient's own bone marrow stem cells as a curative therapy for autosomal recessive hyper-IgE syndrome.
Impact
Demonstration of effective stem cell gene therapy for a gene as large as DOCK8 opens the door for this approach in many other human diseases due to mutations in similarly large genes.
Major Proposed Activities
["Develop and evaluate a gene addition approach for DOCK8 using lentiviral vectors.", "Develop and evaluate a CRISPR-based targeted gene editing approach to site-specifically correct all defects in DOCK8."]
Statement of Benefit to California:
There is no curative treatment for patients with autosomal recessive hyper-IgE syndrome without a bone marrow match or with comorbidities that make them too ill for transplant. Gene corrected HSC may represent a cure for AR-HIES and provides a therapeutic option with fewer inherent risks. This proposal will not only advance the field of stem cell gene therapy and treatment of primary immunodeficiencies but also demonstrate there can be gene therapy options for diseases involving any gene size.