VOLUME 6 | JUNE 2007 | Antonin de Fougerolles, Hans-Peter Vornlocher, John Maraganore and Judy Lieberman
RNA interference (RNAi) has emerged as a powerful tool for gene silencing, revolutionizing biological research and drug discovery. This article discusses the development of RNAi-based therapeutics, focusing on the design and optimization of small interfering RNA (siRNA) molecules, their delivery methods, and clinical progress. SiRNA-based therapeutics offer a novel approach to treating diseases by targeting 'undruggable' genes. The process involves in vitro lead design, in vivo pre-clinical testing, and clinical trials. Key considerations include potency, specificity, and nuclease stability of siRNAs. Delivery methods, such as liposomes, peptides, polymers, and antibodies, are crucial for effective siRNA delivery to target tissues. Clinical trials have shown promising results in treating age-related macular degeneration (AMD) and respiratory syncytial virus (RSV) infections. Despite these advancements, challenges remain, including optimizing siRNA stability and minimizing off-target effects. The article concludes by highlighting the rapid progress of RNAi therapeutics from research to clinical trials, emphasizing the potential of this approach in treating a wide range of diseases.RNA interference (RNAi) has emerged as a powerful tool for gene silencing, revolutionizing biological research and drug discovery. This article discusses the development of RNAi-based therapeutics, focusing on the design and optimization of small interfering RNA (siRNA) molecules, their delivery methods, and clinical progress. SiRNA-based therapeutics offer a novel approach to treating diseases by targeting 'undruggable' genes. The process involves in vitro lead design, in vivo pre-clinical testing, and clinical trials. Key considerations include potency, specificity, and nuclease stability of siRNAs. Delivery methods, such as liposomes, peptides, polymers, and antibodies, are crucial for effective siRNA delivery to target tissues. Clinical trials have shown promising results in treating age-related macular degeneration (AMD) and respiratory syncytial virus (RSV) infections. Despite these advancements, challenges remain, including optimizing siRNA stability and minimizing off-target effects. The article concludes by highlighting the rapid progress of RNAi therapeutics from research to clinical trials, emphasizing the potential of this approach in treating a wide range of diseases.