COMPUTATIONAL VALIDATION OF THE THERAPEUTIC POTENTIAL AND TARGET INTERACTIONS OF WRIGHTIA TINCTORIA AGAINST PSORIASIS-ASSOCIATED RECEPTORS

Abstract

CRISPR-Cas9 has revolutionized genome engineering by providing a simple, programmable, and efficient method to introduce targeted DNA double-strand breaks (DSBs), enabling gene disruption, correction, and precise sequence replacement. Since the adaptation to mammalian genome editing slightly more than a decade ago, CRISPR-Cas9 has passed through a violent storm of development since it was first pioneered in their bench-top tests through demonstrations of the protein in clinical trials. Being a field of translational research, this paper provides a summary of the current state of CRISPR-Cas9 and with a particular focus on therapies of monogenic blood diseases, inherited diseases (metabolic and ophthalmic) and novel potential applications of this technology in oncology and neurology. We address important clinical milestones, technology delivery, technology editing and safety problems including off target activity, immune response and genotoxicity. We describe a representative mixed-method study design that can be used to evaluate the issue of translational readiness through combining the systematic review of the databases of clinical trials and peer-reviewed publications with the extensive analysis of advisory approvals and trial outcomes. New trial reports and regulatory announcements are the key data sources in our primary data collection as well as they assist us in the measurement of indicators of clinical efficacy, the summarization of adverse events, and exploration of the implementation barriers. Key findings indicate that the ex vivo CRISPR-based therapies of hematopoietic stem cells using autologous sources have been profoundly effective in the attenuation of the disease load of sickle cell disease and b-thalassemia with promising safety records, leading to regulatory grants in major jurisdictions. In vivo delivery, off targets, off-target detection and mitigation, long-term monitoring, manufacturing scale and equitable access is challenging. We mean technological and regulation innovation, which could shape the next five years of CRISPR translational research and end with practical recommendations on how to accelerate safe and equitable clinical use.