Aptamers

Aptamers are single-stranded RNA or DNA molecules capable of folding into complex secondary and tertiary structures. They have affinities and specificities comparable to or superior to those of monoclonal antibodies and can be used in both therapeutic and diagnostic applications, including delivery systems for small molecules or gene payloads such as RNAi.

The Aptamer Group at CIMA, University of Navarra, part of the Cancer Center Clínica Universidad de Navarra and led by Fernando Pastor, focuses its research on the generation of aptamers with different therapeutic applications, devoting much of its development to immunotherapy, with the aim of inducing and enhancing the anti-tumor immune response.

The group has developed antagonist and agonist aptamers targeting multiple immune receptors, including CD3, TIM3, LAG3, ICOS, CD28, and CD40, modulating their function according to therapeutic requirements. In addition, it works on the design of “riboswitches” or RNA gene switches, which allow the expression of a transgene to be controlled by inducers capable of changing the conformation of the gene switch. It also develops intracellular aptamers, capable of delivering therapeutic payloads within target cells, ranging from siRNA to other aptamers.

The group has extensive experience in aptamer selection methods, both in vitro and in vivo, applying classic SELEX strategies, targeted selection in cells, and in vivo selection in experimental models, combining bioinformatic analysis tools to prioritize the best aptamers. These methodologies allow the identification of molecules with high affinity and specificity, optimizing their functionality and therapeutic potential.

Within its lines of research in immunotherapy, the group has a special interest in elucidating how the nonsense-mediated mRNA decay (NMD) pathway acts as a critical regulator of tumor antigenicity. As part of this research, RNAi-conjugated aptamers are being developed to selectively inhibit the NMD pathway, increasing the visibility of tumors to the immune system and enhancing the antitumor response.