AAV-dCas9 Epigenetic Editing for CDKL5 Deficiency Disorder
Grant Award Details
Grant Type:
Grant Number:
DISC2-13417
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$1,429,378
Status:
Active
Progress Reports
Reporting Period:
Year 2
Grant Application Details
Application Title:
AAV-dCas9 Epigenetic Editing for CDKL5 Deficiency Disorder
Public Abstract:
Research Objective
We propose a gene therapy for the treatment of a severe infantile epilepsy called CDKL5 Deficiency Disorder using CRISPR-mediated epigenetic editing
Impact
A transformative treatment for females affected by CDKL5 Deficiency Disorder in addition a platform for the approximately 38 other X-linked intellectual disabilities that predominately affect females
Major Proposed Activities
We propose a gene therapy for the treatment of a severe infantile epilepsy called CDKL5 Deficiency Disorder using CRISPR-mediated epigenetic editing
Impact
A transformative treatment for females affected by CDKL5 Deficiency Disorder in addition a platform for the approximately 38 other X-linked intellectual disabilities that predominately affect females
Major Proposed Activities
- Validation of CRISPRe in CDD human neuronal cell models
- Safety and Off-Target profile of CRISPRe in CDD human neuronal cell models
- Rescue of behavioral and functional outcome measures in two mouse models of CDD following CRISPRe administration
- Molecular and Histological Characterization following CRISPRe administration in two mouse models of CDD
- Safety of CRISPRe in two mouse models of CDD
Statement of Benefit to California:
CDKL5 Deficiency Disorder (CDD) occurs in 1 of 40,000 live births meaning there are ten CDD patients born in California each year. CDD has a drastic impact on the quality of life for both the patient and caregiver. Over 43,000 people in California have an intellectual disability. A high number of causative genes for intellectual disabilities are found on the X chromosome. This grant will not only develop a treatment for CDD but may provide a roadmap to treat other X linked disorders.