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Bio-Inspired Approach to RNA Delivery

저자:   업로드:2017-09-22  조회수:

    By delivering strands of genetic material known as messenger RNA (mRNA) into cells, researchers can induce the cells to produce any protein encoded by the mRNA. This technique holds great potential for administering vaccines or treating diseases such as cancer, but achieving efficient delivery of mRNA has proven challenging.

    Now, a team of MIT chemical engineers, inspired by the way that cells translate their own mRNA into proteins, has designed a synthetic delivery system that is four times more effective than delivering mRNA on its own.

    "If we want to be able to deliver mRNA, then we need a mechanism to be more effective at it because everything that's been used so far gives you a very small fraction of what would be the optimal efficiency," says Paula Hammond, Ph.D., a David H. Koch Professor in Engineering, the head of MIT's department of chemical Engineering, and a member of MIT's Koch Institute for Integrative Cancer Research.

    Dr. Hammond is the senior author of a paper (“Polyamine-Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery”) that appears in Angewandte Chemie.

    “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,” write the investigators.

    “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.”

    mRNA is appealing as a potential vehicle to treat disease or deliver vaccines because after an mRNA strand is translated into the desired protein, it eventually degrades. But mRNA first has to get into cells and, once there, it needs to reach the ribosomes to be translated into protein. In a previous study, the MIT team showed it could improve the rate of mRNA translation by attaching a protein cap to one end of the mRNA strand. This cap helps mRNA to form a complex that is needed to initiate translation.

    In the

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