Opening the Intracellular Target Universe to Biologic Drugs

摘要

The development of biologic drugs from the macromolecules of biology, DNA, RNA, and proteins, has led to exciting new disease therapies. A current grand challenge in the biopharmaceutical world is delivering biological macromolecules such as RNA and peptides that work via intracellular drug targets. Here, pH-responsive carriers have been developed for biomolecular drugs that must reach intracellular targets for pharmaceutical activity. These carriers reversibly display membrane destabilizing activity at endosomal pH values to enhance transport of siRNA, DNA, peptides, and proteins to the cytosolic compartment. The reversible addition-fragmentation chain transfer (RAFT) polymerization technique1 from a functionalized chain transfer agent (CTA) has allowed new controlled functionality and architecture control with these carriers.