RNAi-based drug design: considerations and future directions

Read about the design of therapeutic siRNAs, including chemistry, the application of informatics, delivery strategies and the importance of target selection in this Review in the May issue 

  • Qi Tang
  • Anastasia Khvorova
Review Article



    • Drug discovery and development for inflammatory bowel disease (IBD) is hampered by various challenges including the insufficient mechanistic understanding of IBD immunopathology, disease heterogeneity, inadequate preclinical models and clinical trial inefficiencies. This Perspective assesses these limitations and presents strategies to overcome them, including the integration of artificial intelligence and machine learning approaches, organoid technology and innovative trial designs.

      • Sailish Honap
      • Vipul Jairath
      • Laurent Peyrin-Biroulet
    • Secondary pharmacology screening of investigational small-molecule drugs for potentially adverse off-target activities is now standard practice in pharmaceutical research and development. This article uses a survey across 18 companies as the basis for discussing strategies for implementing secondary pharmacology screening programmes, approaches for interpreting off-target activities and which targets to include in screening panels, including several targets not commonly included in existing panels.

      • Richard J. Brennan
      • Stephen Jenkinson
      • Jean-Pierre Valentin
    • The rise of drug resistance presents a significant challenge in the treatment of infectious diseases. This Review summarizes the status and mechanisms of drug resistance in malaria, human immunodeficiency virus (HIV) infection and tuberculosis, and explores strategies to address resistance that could be incorporated into drug development across these disease areas.

      • Maëlle Duffey
      • Robert W. Shafer
      • Didier Leroy
      Review Article
    • RNA has revolutionized modern medicine, creating great expectations. However, challenges with this class of drugs persist. In this Review, John Androsavich analyses lessons learnt from RNA modalities such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNA), and discusses strategies to develop RNA drug platforms, improving their applicability, efficacy and safety profiles.

      • John R. Androsavich
      Review Article
    • Immunogenic cell death (ICD) is crucial for the elicitation of anticancer immune responses by therapy, but the successful development of ICD-inducing treatments is hindered by various obstacles. This Review provides an overview of the core mechanisms of ICD, discusses obstacles to the development of novel ICD modulators and assesses established and innovative therapeutic approaches for ICD induction.

      • Lorenzo Galluzzi
      • Emma Guilbaud
      • Francesco M. Marincola
      Review Article


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