Enhancing the safety of CRISPR-based therapeutics for human genetic disease
Name of applicant
Rasmus Møller
Title
Postdoctoral Fellow
Institution
Enceladus Bio Inc.
Amount
DKK 2,006,370
Year
2024
Type of grant
Reintegration Fellowships
What?
Editing the human genome for therapeutic purposes to cure genetic diseases has recently become a reality by utilizing CRISPR/Cas technology; a system capable of editing any specific sequence in our DNA. This project presents a method to enhance the specificity and accuracy of gene editing by limiting its activity to a particular cell type reducing the risk of unwanted off-target effects.
Why?
While the genome of human cells can be edited with high efficiency, unwanted off-target effects are often described. These can either be edits of unintended genes or edits in distal tissues unaffected by the disease. Off-target edits can produce malignant cells or occur in the germ line and be passed onto future generations, causing serious safety concerns from a regulatory standpoint.
How?
Each cell type has a unique expression pattern of a type of small RNAs called micro-RNAs (miRNA). By making CRISPR/Cas activity dependent on miRNAs, gene editing by CRISPR/Cas can be restricted to any desired cell type or tissue as long as it is characterized by a unique miRNA. This will improve safety of any CRISPR-based approach being developed as a therapeutic candidate.