The review’s abstract describes recent progress in identifying novel Cas orthologs and engineering Cas9 variants to improve editing fidelity, expand target ranges and reduce off-target effects. It also reports that structural and functional optimization of single-guide RNAs has improved target-binding affinity, stability and formation of the Cas9-sgRNA complex. High-fidelity Cas9 derivatives, base editors and prime editors are presented as enabling precise single-nucleotide substitutions and small insertions or deletions without producing double-stranded DNA breaks.

Delivery remains a central focus. According to the abstract, viral vectors, lipid nanoparticles and ribonucleoprotein electroporation have advanced CRISPR-mediated editing across in vitro, ex vivo and in vivo models. The review highlights therapeutic milestones reported for sickle cell disease, β-thalassemia and cystic fibrosis, where the abstract states that long-term clinical benefits have been documented. It also identifies a separate research role for CRISPR-Cas9 in diabetes: modeling disease mechanisms, identifying molecular pathways involved in glucose homeostasis and supporting development of cellular and gene-based therapies.

This is a review rather than a new clinical trial, laboratory study or protocol, and the available evidence consists of the article’s abstract and publisher information rather than the full text. The abstract does not provide study populations, sample sizes, quantitative editing efficiencies, delivery-performance measures, follow-up periods, safety outcomes or a systematic assessment of the cited clinical evidence. Consequently, the reported therapeutic milestones and broader translational claims are summarized here as the review’s conclusions; the available source does not support independent verification of their magnitude or applicability to individual patients.

Subject of Research: CRISPR-Cas9 genome editing technologies, delivery systems and therapeutic applications

Article Title: CRISPR–Cas9 genome editing: technological advances, delivery strategies and precision engineering of primary cells for therapeutic application in genetic disorders and diabetes mellitus

Article References: Islam, M. N., Islam, M. M., Feng, H., Bellah, S. F., Zaman Miah, M. M., & Hossain, M. S. (2026). CRISPR–Cas9 genome editing: technological advances, delivery strategies and precision engineering of primary cells for therapeutic application in genetic disorders and diabetes mellitus. Molecular Biology Reports, 53(1), Article 1589. https://doi.org/10.1007/s11033-026-12771-1

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12771-1

Keywords: CRISPR-Cas9, genome editing, base editing, prime editing, gene delivery, primary cells, genetic disorders, sickle cell disease, β-thalassemia, cystic fibrosis, diabetes mellitus, CRISPR