Genome Editing Beyond Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR): Comparative Insights into Alternative Tools

2026-01-30T11:53:10+00:00

Genome editing has been revolutionized by the introduction of CRISPR–Cas systems, which, in a very short time, became the main tools in both research and clinical pipelines. Nevertheless, CRISPR-based methods have their limitations. Unintended targeting, protospacer adjacent motif (PAM) requirements, delivery difficulties, and possible immunogenicity are still the main challenges for a widely safe application. These limitations have led to the revival of older genome-editing technologies such as meganucleases, zinc-finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs), as well as to newer inventions like base editors and prime editors. This review covers alternative genome-editing platforms that go beyond the use of classical CRISPR nucleases. The discussion covers molecular mechanisms, applications, and performance compared to CRISPR systems. Delivery strategies, such as viral, non-viral, and mRNA/RNP approaches, are examined along with their suitability for ex vivo and in vivo applications. Clinical case studies, including CCR5 editing for HIV, hemoglobinopathies, and in vivo therapies for liver and eye disorders, demonstrate real-world applications. Ethical and regulatory issues are also addressed, particularly regarding germline versus somatic editing, patient consent, long-term monitoring, and international policies. Analysis reveals that no single approach is best in all cases, and the choice of tools depends largely on the biological question or therapeutic goal. Next steps for these technologies include combining and refining methods and further developing the genome-editing toolkit to ensure safe and efficient clinical translation.

Pharmacological Management of Benign Thyroid Nodules: A Comprehensive Systematic Review of Repurposed Therapeutics and Molecular-Targeted Strategies

2026-02-26T07:08:12+00:00

Background: Benign thyroid nodules are highly prevalent, affecting approximately 50–60% of adults on high-resolution ultrasonography. Despite their frequency, management remains limited to surveillance, minimally invasive ablative techniques, or surgery. Earlier levothyroxine-based thyroid-stimulating hormone (TSH) suppression showed inconsistent efficacy and adverse metabolic effects, limiting its role in current clinical practice. Objective: This systematic review synthesizes evidence from clinical trials, preclinical studies, and epidemiological data to evaluate emerging pharmacological therapies for benign thyroid nodules. It focuses on TSH-modulating agents, selective THR-β agonists, mTOR pathway modulators, antifibrotic and vascular-targeted therapies, and mutation-specific agents, with particular emphasis on drug repurposing. Methods: A comprehensive search of PubMed, Scopus, Web of Science, and Embase (January 2000–December 2025) identified relevant clinical, preclinical, and observational studies. Data extraction focused on nodule volume reduction, safety profiles, and mechanistic insights from thyroid cell cultures, organoid models, and murine experiments. Study quality was assessed using standardized tools. Results: Levothyroxine achieved a 10–20% mean volume reduction in 1,245 patients, but caused hyperthyroidism in 14–19% of patients. Selective THR-β agonists produced a 21% reduction with improved safety over 24 weeks (n=48). Mutation-directed therapies targeting RET, BRAF, and NTRK yielded 25–32% reductions in preliminary cohorts. mTOR inhibitors achieved an 18% reduction with acceptable tolerability (n=12). Repurposed agents such as metformin (16% reduction, n=67) and statins (22% reduced prevalence in observational studies) showed moderate efficacy and favorable safety. Antifibrotic therapies demonstrated promising preclinical results, reducing fibrotic markers by 35–45%. Conclusion: Evidence supports a shift from observation-only strategies toward precision pharmacotherapy for selected benign thyroid nodules. Repurposing established drugs with known safety profiles offers the most feasible near-term approach, while molecular stratification may improve targeted treatment effectiveness and address an unmet need in endocrinology practice.

International Journal of Modern Pharmacy and Life Sciences

Genome Editing Beyond Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR): Comparative Insights into Alternative Tools

Pharmacological Management of Benign Thyroid Nodules: A Comprehensive Systematic Review of Repurposed Therapeutics and Molecular-Targeted Strategies