Work

Comparing CRISPR-Cas9 Gene Therapy Delivery Systems: Implications and Optimization for Hyperargininemia

Year: 2025

Type: article

Abstract: Hyperargininemia is a rare autosomal recessive metabolic disorder caused by a deficiency in the urea cycle enzyme arginase 1, resulting in severe systemic and neurological complications. Given the shortcomings of conventional treatment paradigms, there is an increasing demand for gene therapies, such as CRISPR-Cas9, that address hyperargininemia at its genetic root and reverse its diverse manifestations. Homology-directed repair offers high specificity and durable genetic correction. The strategic delivery of CRISPR components, including homology arm-flanked, wild-type ARG1 cDNA, Cas9 endonucleases, and appropriate sgRNAs, is necessary to enable homology-directed repair in arginase 1-deficient hepatocytes. This review summarizes the methodology, strengths, and weaknesses of three prominent CRISPR delivery methods: lipid nanoparticles, recombinant adeno-associated viruses, and electroporation. We also highlight ongoing efforts to optimize these delivery methods and analyze the relevance of existing preclinical CRISPR-Cas9 studies to hyperargininemia. Among these delivery systems, recombinant adeno-associated viruses currently show the most promise for clinical translation, although further enhancements in safety and scalability remain necessary.

Source: Precision Nanomedicine

DOI: 10.33218/001c.153885

Authors: Jad Madani, Humza N. Zubair, Ghazi A. Saroya, Rachel E.N. Reyes, Rami Madani

Institutions: University of California, Los Angeles, Western Michigan University, Children's Hospital of Los Angeles, Saban Research Institute

Language: English

Topic: CRISPR and Genetic Engineering

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

OpenAlex ID: W4417064281