Work

Polyamine‐Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery

Year: 2017

Type: article

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.

Source: Angewandte Chemie

DOI: 10.1002/ange.201707466

Authors: Jiahe Li, Yanpu He, Wade Wang, Connie Wu, Celestine Hong, Paula T. Hammond

Institutions: Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Science Foundation, U.S. Department of Defense, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Defense Advanced Research Projects Agency