The Third Pillar of Precision Medicine - Precision Delivery

Precision Medicine is thought of as having two main pillars: Precision Diagnosis and Precision Therapy. However, for Precision Medicine to reach its full potential, a third pillar is needed that we propose to call Precision Delivery. In the laboratory, many therapies show great efficacy when tested directly with target cells. However, upon clinical translation, they are often given via intravenous or oral administration, resulting in their systemic distribution. To ensure therapies reach target sites at the correct therapeutic levels, they are often given at higher concentrations. However, this can be associated with off-target effects, side-effects, and unwanted interactions. Delivery strategies can help mitigate this by "spatially re-coupling" therapies in vivo with target cells. This review explains the concept of Precision Delivery, which can be thought of as three interconnected, but independent, modules: targeted delivery, microenvironment modulation, and cellular interactions. While locoregional approaches directly deliver therapies into target tissues through endovascular, endoluminal, percutaneous, and implantation techniques, microenvironment modulation technologies facilitate the movement of therapies across biological barriers and through tissue matrices, so optimized therapies can reach and interact with target cells. We highlight new innovations driving advances in Precision Delivery, while also discussing the considerations and challenges that Precision Delivery faces as it becomes increasingly integrated into treatment workflows.