Comment in 2026

As pressure mounts globally on drug pricing and development cost continues to rise, clinicians and translational scientists in biotech, academia and biopharma companies are re-evaluating when, where and how to launch early clinical programs. These initial patient data become critical to de-risk development programs and allow developers to deploy their limited time and resources on the most promising drugs. We evaluate four fundamental shifts in drug development that appear to be unfolding and may well become critical to future global biopharma success: use of large-scale high quality cohort studies, sponsor-driven investigator-initiated trials, the integration of affordable artificial intelligence with extensive high quality data registries, and China’s focus on precision medicine. —

Immunotherapy is at an inflection point. After three decades of accelerating progress, immunotherapy is entering the realm of in vivo engineering. This Comment discusses the potential of in vivo engineering in addressing challenges met by ex vivo engineering efforts. Per a recent workshop organized by the National Institutes of Health, we highlight progress, the platform technologies fueling it, and elements of a road map and challenges ahead.

Our understanding of the genetic mechanisms underlying rare diseases has rapidly advanced over the past decade, largely because of technological innovations. Yet clinical practice still has a strong monogenic focus, leaving many individuals undiagnosed. This Comment outlines how technological advances such as long-read sequencing should be adopted to increase multivariant testing in the clinic.