Abhishek Aditham (ZHANG & WANG LABS)

Modification of mRNA Poly(A) Tails to Augment Expression

Therapeutic mRNA has recently emerged as a new platform for vaccine development. Despite recent advances in therapeutic mRNA engineering, the platform remains limited in its utility by its relatively short lifetime. Chemical modification of nucleotides is a promising method to increase nucleic acid stability, and is frequently used in engineered anti-sense oligos (ASOs). Here we describe a strategy to augment therapeutic mRNA stability by engineering poly(A) tails with enhanced nuclease resistance.

Kalon Overholt (LAUFFENBURGER, DEL VECCHIO & YOUNG LABS)

Uncovering Chemical Rules for Small Molecule Partitioning in Protein-Rich Compartments

The cell is a heterogeneous environment where areas rich in specific functional proteins compartmentalize distinct biological processes. In drug development applications, understanding how small molecules partition into subcellular compartments may guide rational design. Here, we develop a screening platform to measure small molecule affinity for marker proteins of nucleolar, heterochromatin, and transcriptional compartments. Leveraging these data, we begin to uncover structure-based rules dictating the partitioning behavior of small molecules.