EMERGING GENE THERAPY APPROACHES LEVERAGING CRISPR TECHNOLOGIES FOR TREATMENT OF INHERITED GENETIC DISORDERS

Abstract

Background: Inherited genetic diseases are associated with millions of people in the world and this occurs due to the single-gene mutations. Standard treatments, such as viral gene replacement, have limitations in the form of transient expression, insertional mutagenesis, and a lack of precision.

Objective: The study seeks to review the novel CRISPR-based gene therapy methods of correcting mutations leading to diseases and enhancing the efficacy of therapy.

Methodology: A systematic search of recent preclinical and clinical studies was done, covering CRISPR-Cas9, base editing and prime editing methods and strategies were being applied through in vivo and ex vivo systems. Among the important measurements considered were the susceptibility of editing and rates off-target and phenotypic correction.

Findings: CRISPR-Cas9 had an up to 8090% editing efficiency in ex vivo hematopoietic stem cells and base editing had a much more specific nucleotide fixing capability with a lower off-target implication (12-4%). Prime editing demonstrated versatile mutation repairing capabilities, albeit with medium efficiencies (2050%). The in vivo delivery with lipid nanoparticles and with AAV vectors demonstrated better tissue targeting yet inconsistent efficiency. In general, the restoration of phenotypes was high in such disorders as sickle cell disease and Duchenne muscular dystrophy.

Conclusion: CRISPR-based gene therapies promise to transform potential treatment of inherited diseases, being more precise and safe. Nonetheless, there are still issues related to optimization of delivery, long-term safety, and ethical issues.