Editors' ChoiceNanomedicine

The mRNA “game changer” in gene therapy

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Science Translational Medicine  03 Feb 2016:
Vol. 8, Issue 324, pp. 324ec21
DOI: 10.1126/scitranslmed.aaf2008

Gene therapy promises to correct genomic aberrations and treat many human illnesses, especially owing to the advent of CRISPR/Cas9 technology, a gene editing tool. Another gene therapy technology that involves nanoparticle delivery of nucleic acids, such as mRNA and siRNA, which alter gene expression is also rapidly maturing and may rival the impact of CRISPR/Cas9. The clinical translation of mRNA and siRNA has been limited by the lack of effective delivery vehicles. To address this, Dong et al. engineered a new type of nanoparticle using a polymer-brush material poly(glycoamidoamine). The positively charged amino groups bound to the negatively charged nucleic acids, and alkyl tail brushes were added onto the polymer backbone to allow incorporation of the polymer into a lipid-based nanoparticle formulation. The authors demonstrated that nanoparticles formulated using this material could efficiently deliver siRNA and mRNA systemically and were nontoxic. Mice receiving human erythropoietin (EPO) mRNA in nanoparticles expressed 1000-fold more EPO mRNA than when given free EPO mRNA. In addition, nanoparticle delivery of siRNA against the gene encoding Factor VII, a key protein involved in the clotting cascade, demonstrated significant reduction in FVII levels in the mice. The next step will be treating disease with these nanoparticle-formulated nucleic acids, which will make such technology attractive to several pharmaceutical companies already looking to bring RNA therapeutics to clinical practice.

Y. Dong et al., Poly(glycoamidoamine) brushes formulated nanomaterials for systemic siRNA and mRNA delivery in vivo. Nano Lett. 10.1021/acs.nanolett.5b02428 (2016). [Abstract]

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