RNA therapies

Frameworks for transformational breakthroughs in RNA-based medicines

Read about strategies for developing RNA drug platforms, including layering technologies, addressing common biases and identifying gaps in understanding in this Review in the June issue

  • John R. Androsavich
Review Article

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    • Deeper pharmacological characterization of hit and lead compounds is being enabled by novel assays to characterize target behaviour as well as by advances in structural biology. This article discusses key factors in pharmacological characterization in the context of G protein-coupled receptors as a target class, highlighting opportunities to identify drug candidates with the potential to address limitations of current therapies and to increase the probability of them succeeding in clinical trials.

      • Terry Kenakin
      Perspective
    • Advances in understanding of the cause of autoimmune diseases and clinical data from novel therapeutic modalities such as chimeric antigen receptor T cells are providing evidence that it may be possible to re-establish immune homeostasis and, potentially, prolong remission or even cure autoimmune diseases. This article proposes a three-step ‘sequential immunotherapy’ framework for immune system modulation to help achieve this ambitious goal, and discusses existing drugs and those in development for each of the three steps.

      • Francisco Ramírez-Valle
      • Joseph C. Maranville
      • Robert M. Plenge
      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
      Perspective
    • 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
      Perspective
    • 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
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