Therapeutic antibody delivery: vector tools to boost efficacy and affordability

Antibody (Ab)-based therapeutics have become powerful tools across diverse disease areas, with advances in bioengineering giving rise to next-generation molecules designed to outperform conventional Abs. Yet, large-scale production and purification of such complex proteins remain costly and can restrict patient access. A promising alternative is to improve <i>in vivo</i> expression capabilities, which will reduce manufacturing burdens and improve safety and tolerability. Multiple gene delivery platforms - ranging from mRNA and viral vectors to engineered cell therapies - have matured considerably, as a direct result of years of clinical experience and growing regulatory confidence. The rapid deployment of mRNA vaccines against SARS-CoV-2, the clinical success of adeno-associated virus (AAV)- and lentiviral-based interventions, and the approval of chimeric antigen receptor (CAR)-T cell therapies highlight the potential of these technologies to transform how we deliver Ab therapeutics. While these approaches hold the promise to treat genetic aberrations in patients, they may also contribute considerably to advancing conventional Ab therapeutics against viral infections and other diseases through local persistence of the proteins. Looking forward, <i>in situ</i> expression may confer even more benefits for engineered Ab-like molecules, thereby compensating for possibly shorter half-lives and overcoming challenges in <i>in vitro</i> production and purification. Therefore, in this review, we critically evaluate how these established and emerging gene therapy platforms can be harnessed to expand access, and discuss possibilities to improve <i>in situ</i> availability through the choice of transient or stable expression systems to increase the efficacy of Abs and other therapeutic proteins. Furthermore, we explore the current landscape of technological advancements, identify key translational challenges, and project future directions for optimizing these approaches towards widely applicable clinical interventions.