Polyamine‐Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery
Abstract
Messenger RNA (mRNA) represents a promising class of nucleic acid drugs. Although numerous carriers have been developed for mRNA delivery, the inefficient mRNA expression inside cells remains a major challenge. Inspired by the dependence of mRNA on 3′‐terminal polyadenosine nucleotides (poly A) and poly A binding proteins (PABPs) for optimal expression, we complexed synthetic mRNA containing a poly A tail with PABPs in a stoichiometric manner and stabilized the ribonucleoproteins (RNPs) with a family of polypeptides bearing different arrangements of cationic side groups. We found that the molecular structure of these polypeptides modulates the degree of PABP‐mediated enhancement of mRNA expression. This strategy elicits an up to 20‐fold increase in mRNA expression in vitro and an approximately fourfold increase in mice. These findings suggest a set of new design principles for gene delivery by the synergistic co‐assembly of mRNA with helper proteins.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 19, 2017
- Source ID
- 10.1002/ange.201707466
Entities
People
- Celestine Hong
- Connie Wu
- Jiahe Li
- Paula T. Hammond
- Wade Wang
- Yanpu He
Organizations
- Defense Advanced Research Projects Agency
- Massachusetts Institute of Technology