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Targeting Undruggable Proteins: The siRNA Revolution Beyond Small Molecules - Advances, Challenges, and Future Prospects in Therapeutic Innovation

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dc.contributor.authorJan, SK Ashif
dc.contributor.authorDebnath, Abhijit
dc.contributor.authorSingh, Rajesh Kumar
dc.contributor.authorTyagi, Pankaj Kumar
dc.contributor.authorSingh, Sachin
dc.contributor.authorSingh, Anil Kumar
dc.date.accessioned2025-07-09T06:29:02Z
dc.date.available2025-07-09T06:29:02Z
dc.date.issued2025
dc.description.abstractThe field of drug discovery has long been challenged by the existence of “undruggable” proteins - targets that have resisted traditional small molecule approaches due to their structural or functional characteristics. This review explores the revolutionary potential of small interfering RNA (siRNA) technology in addressing these elusive targets, marking a paradigm shift in therapeutic development. We discuss the historical development of siRNA technology and its unique mechanism of action, which allows for the silencing of virtually any gene, including those coding for proteins previously deemed undruggable. The review provides a comprehensive analysis of the challenges in targeting undruggable proteins and how siRNA approaches are overcoming these obstacles. We examine several case studies of undruggable targets being successfully addressed by siRNA, including oncogenic proteins like KRAS and c-Myc, transcription factors such as NF-κB and STAT3, and proteins involved in complex protein-protein interactions. The article delves into the latest advances in siRNA design, delivery systems, and targeting strategies, highlighting innovations that enhance specificity and reduce off-target effects. We also discuss the challenges facing siRNA therapeutics, including delivery obstacles, potential immune responses, and regulatory considerations. The review concludes with an exploration of future directions, including combination therapies, personalized medicine approaches, and emerging technologies that complement siRNA strategies. By providing a thorough examination of the advances, challenges, and prospects of using siRNA to target undruggable proteins, this review underscores the transformative potential of this technology in expanding the landscape of therapeutic targets and ushering in a new era of precision medicine. © 2025 Bentham Science Publishers.
dc.identifier.doihttps://doi.org/10.2174/0115665232357160250123113148
dc.identifier.issn15665232
dc.identifier.urihttps://dl.bhu.ac.in/ir/handle/123456789/112984
dc.publisherBentham Science Publishers
dc.subjectdrug discovery
dc.subjectgene silencing
dc.subjectmolecular targeted therapy
dc.subjectRNA interference
dc.subjectsiRNA
dc.subjectsiRNA drug delivery
dc.subjectsmall interfering RNA
dc.titleTargeting Undruggable Proteins: The siRNA Revolution Beyond Small Molecules - Advances, Challenges, and Future Prospects in Therapeutic Innovation
dc.typeReview
dspace.entity.typePublication
journal.titleCurrent Gene Therapy

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