AI-Powered CRISPR-Cas9: Precision Therapeutics for ATP7B Mutations in Wilson Disease and Restoring Copper Metabolism.

Introduction: Wilson Disease is a genetic disorder caused by a mutation in ATP7B gene that leads to toxic copper accumulation in vital organs such as the liver, brain, kidneys, and eyes. The copper overload results in severe liver dysfunction, neurological problems, kidney impairment, and the hallmark feature called KayserFleischer rings in the eyes, which becomes progressively life-threatening if left untreated. With recent technological advancements, this research aims to explore the potential of using Artificial Intelligence (AI) with CRISPR-Cas9 gene-editing technology to develop precision therapies for correcting ATP7B mutations (28, 29). Methods: A comprehensive thorough literature review was conducted using free access databases such as PubMed and Google Scholar. Keywords used in the search were "Wilson Disease," "ATP7B mutations," "CRISPR-Cas9," "gene editing," "AI in gene therapy," and "copper metabolism." The review included studies involving AI-powered CRISPR-Cas9 applications in cellular and animal models (28). Also, articles exploring AI's role in enhancing CRISPR precision and identifying ATP7B mutations were included (43, 44). Results: CRISPR/Cas9 has shown significant success in correcting ATP7B mutations linked to Wilson Disease through gene editing in both cellular and animal models (28). Notably, studies involving Wilson Disease model rabbits, where specific mutations were introduced via CRISPR, have revealed hallmark symptoms such as copper accumulation in the liver (28). CRISPR technology has been used to repair the ATP7B R778L mutation in human iPSC-derived hepatocytes, restoring copper metabolism in vitro (28). These gene-corrected cells were transplanted into animal models, offering a potential therapeutic solution. CRISPR also enhances diagnostic capabilities, enabling precise identification of ATP7B mutations (41, 47). While challenges such as off-target effects and delivery efficiency remain, advancements in gene-editing precision and the integration of AI could significantly improve the efficacy and personalization of treatments (43, 45). Conclusion: AI-powered CRISPR-Cas9 therapies show promising potential in correcting ATP7B mutations and restoring copper metabolism in Wilson Disease cases (29, 49). Despite challenges such as cost and the inability to deliver the corrected gene precisely to the large number of affected patients, integrating AI may enhance accuracy and personalization, leading to safer, more effective treatments and lasting therapeutic solutions for Wilson Disease (47, 48). [ABSTRACT FROM AUTHOR]