CRISPR-CAS GENOME EDITING IN PHARMACEUTICAL BIOTECHNOLOGY: ADVANCES, THERAPEUTIC APPLICATIONS, CHALLENGES AND FUTURE PERSPECTIVES

Abstract

CRISPR-Cas genome editing has evolved from a bacterial adaptive immune mechanism into a validated pharmaceutical platform spanning drug discovery, direct genetic therapeutics, and molecular diagnostics. This review provides a pharmaceutically oriented synthesis of the technology’s mechanistic foundations, its evolution from first-generation Cas9 nucleases through base editing, prime editing, and CRISPR interference/activation, and its applications across the drug discovery and development pipeline, including target identification, functional genomic screening, and disease modeling. We examine the therapeutic landscape in detail, covering oncology, hematological disorders, infectious disease, and metabolic and neurological conditions, alongside the ex vivo and in vivo gene- and cell-therapy platforms that have brought these approaches to the clinic, exemplified by the regulatory approval of Casgevy and the growing pipeline of in vivo hepatic editing programs. Particular attention is given to the delivery technologies such as viral, non-viral, and lipid-nanoparticle-based that increasingly represent the rate-limiting step in clinical translation, and to CRISPR-based diagnostics and their convergence with precision medicine. This review then addresses the principal challenges constraining pharmaceutical translation, including off-target effects, immunogenicity, genome stability, and manufacturing scalability, together with the ethical and regulatory considerations particularly the somatic-germline distinction and equitable access that shape how these technologies are deployed. We close with an assessment of emerging trends, including artificial-intelligence-assisted guide RNA design and next-generation delivery platforms, prospects for clinical translation, and a discussion of the limitations inherent in synthesizing a rapidly evolving field. Collectively, this review aims to provide researchers and drug developers with a comprehensive, integrated view of CRISPR-Cas technology’s current state and trajectory within pharmaceutical biotechnology.