Volume 18 Issue 6, June 2019

Inhibitors of the innate immune system’s NLRP3 inflammasome promise potential in Parkinson disease, Alzheimer disease, non-alcoholic steatohepatitis, gout and much more, catching the eye of Novartis, Genentech and others.

Despite industry’s past setbacks with autophagy inhibitors, preclinical and clinical findings are starting to revitalize a once written-off strategy.

The recent approval of the first RNA interference (RNAi)-based therapy has generated considerable excitement in the field. Here, Rossi and colleagues discuss key advances in the design and development of RNAi drugs leading up to this landmark achievement, assess the current clinical pipeline and highlight future opportunities and challenges for RNAi-based therapeutics.

Advances in the design of vectors based on retroviruses, such as lentiviruses and gammaretroviruses, have led to improvements in the safety and stability of gene therapies directed at haematopoietic stem and progenitor cells. In this Review, Cavazzana and colleagues discuss the results from recent clinical trials of retroviral vectors for the treatment of genetic disorders, including severe combined immunodeficiencies and β-haemoglobinopathies (β-thalassaemia and sickle cell disease). They highlight the progress made and the remaining challenges in applying gene therapies more broadly.

Machine learning has been applied to numerous stages in the drug discovery pipeline. Here, Vamathevan and colleagues discuss the most useful techniques and how machine learning can promote data-driven decision making in drug discovery and development. They highlight major hurdles in the field, such as the required data characteristics for applying machine learning, which will need to be solved as machine learning matures.