Intracellular mRNA delivery is generally considered to be inefficient due to the transient nature and low stability of extracellular mRNA, leaving the field under developed compared to vectors optimized for other nucleic acids (pDNA, siRNA, etc.). However, recent advances in synthetic mRNA have made mRNA based therapeutics more viable, creating a demand for new delivery vectors.  A dendronized polymer (Denpol) system based off our previous work with siRNA delivery was investigated for the ability to deliver mRNA to the cytoplasm.  The Denpols investigated produced several hits, which perform on par with or better than current commerically available vectors.  Histidine and tryptophan were found to be critical additions to the polymer to enable buffering capacity for endosomal escape and an indole ring for efficient binding to mRNA respectively.  PEGylation of the Denpols also yielded more stable nanoparticles better optimized for mRNA delivery.

Dendronized polymers for mRNA delivery

251st National Meeting (2016)

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