Next-Gen Gene Editing and Programmable Chromosome Engineering for Potential Cancer Gene Mutation Therapeutics

Abstract

Gene editing technologies have revolutionized the approach to treating cancer by enabling precise modifications to the genome, particularly through programmable chromosome engineering techniques that allow for large-scale rearrangements, deletions, and insertions to correct or disrupt cancer-driving mutations. While traditional therapies target symptoms or pathways, next-generation tools like CRISPR/Cas9 derivatives, base editors, and prime editors offer a roadmap for directly addressing oncogenic mutations in genes such as TP53, KRAS, and BRCA1, potentially halting tumour progression at the chromosomal level. This review synthesizes recent advancements by conducting a comprehensive analysis of studies from PubMed, Scopus, and Web of Science, emphasizing applications in solid tumours and hematological malignancies, including the integration of gene editing with CAR-T cell therapies to overcome resistance. This review included peer-reviewed original research articles, clinical trials, and review papers published between 2015 and 2024 that focus on programmable chromosome engineering applied to cancer treatment. Findings indicate that CRISPR-based systems achieve up to 95% efficiency in knocking out cancer-associated genes in preclinical models, with one study demonstrating a 80% reduction in tumour burden in mouse models of lung cancer through targeted chromosome arm deletions. Additionally, programmable editors have successfully corrected point mutations in 85% of patient-derived organoids, linking chromosomal stability to improved therapeutic outcomes. In combination with nanoparticle delivery, these tools enhance specificity, reducing off-target effects to below 5% in recent trials. However, challenges persist, including ethical concerns over germline editing, immune responses to viral vectors, and scalability for personalized medicine. Ongoing efforts focus on developing non-viral delivery systems and AI-guided design for editors to improve predictability. Future directions include phase II clinical trials for CRISPR-engineered therapies in refractory cancers and expanding to rare mutations, fostering collaboration among geneticists, oncologists, and bioengineers to translate these innovations into curative strategies.