Overcoming the Delivery Bottleneck: Can Existing Drug Delivery Technologies Solve CRISPR-Cas9's Biggest Limitation in Treating Inherited Disease?

Authors

Bareera Hajab · Annabelle Kim

Abstract

Inherited diseases arise from mutations in an individual's DNA and are broadly categorised as single-gene defects, chromosomal defects, mitochondrial disorders and multifactorial disorders. Unlike traditional treatments, which largely manage symptoms rather than correct their underlying cause, CRISPR-Cas9 gene editing offers the possibility of a permanent molecular fix. However, clinical translation remains constrained by inefficient cellular delivery, viral packaging limitations, the risk of off-target effects and the ethical concerns surrounding irreversible germline editing. This review examines whether existing drug delivery technologies, particularly lipid nanoparticles (LNPs), can overcome these barriers. Drawing on recent advances in thermostable Cas9 ribonucleoprotein delivery, human clinical trials and engineered extrahepatic organ targeting, we show that delivery systems are not merely incremental improvements but essential enablers for translating CRISPR-Cas9 into viable inherited-disease therapy. Despite this progress, challenges remain in achieving precise targeting across all affected tissues and confirming long-term safety. This review argues that delivery technology, rather than the editing mechanism itself, is now the primary factor determining how soon CRISPR-Cas9 becomes a practical therapy.

Keywords: CRISPR-Cas9, lipid nanoparticles, drug delivery, inherited disease, gene editing

Contact the Authors

Bareera Hajab — barirahhijjab@gmail.com

Annabelle Kim — kim.annabelle08@gmail.com