Multidisciplinary Therapeutic Strategies for Complex Diseases: Nanotechnology, CRISPR, Protein Degradation, and AI Applications

Challenging diseases, including cancer, neurodegeneration and autoimmunity, are characterized by complex pathogenesis and poor response to currently available therapies. The present review discusses promising treatment modalities based on an integrated approach comprising four major technological breakthroughs nanotechnology, CRISPR-Cas9 gene editing, targeted protein degraders and artificial intelligence. Application of nanotechnology allows for targeted delivery of a therapeutic payload across multiple biological barriers with circumvention of the blood-brain barrier and access to the posterior segment of the eye. CRISPR-Cas9-based genome editing corrects the disease-causing genetic variants and recent clinical trials have demonstrated the safety and efficacy of this approach in multiple ocular and hematological genetic disorders. Bifunctional molecules, including proteolysis-targeting chimeras (PROTACs) and heat shock protein 90 (HSP90) inhibitors, are promising modalities for the degradation of disease-associated proteins that are not amenable to traditional small-molecule inhibitors. Finally, artificial intelligence contributes to modern drug discovery and development by accelerating drug formulation and identification of the most effective treatment for application in clinical practice. Combined application of these technologies can tackle complex diseases by targeting several disease determinants simultaneously. Specific examples include immunotherapy of malignancies, treatment of neurodegenerative disorders and ocular gene therapy. Current challenges in the translation of these therapeutic breakthroughs into clinical practice include technolog y scalability, clinical trial design, regulatory framework, drug patent issues and global accessibility. The present paper discusses recent advances in these areas and defines integrated treatment approaches for various diseases.