Abstract
Use of non-biological agents for mRNA delivery into living systems in order to induce heterologous expression of functional proteins may provide more advantages than the use of DNA and/or biological vectors for delivery. However, the low efficiency of mRNA delivery into live animals, using non-biological systems, has hampered the use of mRNA as a therapeutic molecule. Here, we show that gold nanoparticle-DNA oligonucleotide (AuNP-DNA) conjugates can serve as universal vehicles for more efficient delivery of mRNA into human cells, as well as into xenograft tumors generated in mice. Injections of BAX mRNA loaded on AuNP-DNA conjugates into xenograft tumors resulted in highly efficient mRNA delivery. The delivered mRNA directed the efficient production of biologically functional BAX protein, a pro-apoptotic factor, consequently inhibiting tumor growth. These results demonstrate that mRNA delivery by AuNP-DNA conjugates can serve as a new platform for the development of safe and efficient gene therapy.
Highlights
IntroductionMessenger RNA (mRNA) is a promising vehicle for expression of target proteins in both the treatment of genetic diseases and for vaccination (for recent reviews, see 1-3)
Messenger RNA is a promising vehicle for expression of target proteins in both the treatment of genetic diseases and for vaccination
Consistent with previously reported results [20,21], our results showed that approximately one-fourth of the 5′dsRED Messenger RNA (mRNA) in the reaction mixtures were loaded onto AuNP-αRNA I at saturating concentrations of mRNA (Figure 1A, left upper panel)
Summary
Messenger RNA (mRNA) is a promising vehicle for expression of target proteins in both the treatment of genetic diseases and for vaccination (for recent reviews, see 1-3). Compared to plasmid DNA (pDNA)-mediated gene delivery, mRNA-based transfection confers several advantages. MRNA delivery is safer than pDNA delivery, as mRNA does not integrate into the genome, leaving the transfection transient. MRNA does not need to enter the nucleus to perform its function, whereas in pDNA delivery, the nuclear membrane presents as a major barrier. Transcriptional initiators (promoters) and terminators are dispensable for synthetic mRNAs, making them relatively easy to engineer for therapeutic molecules. Taken together, these features demonstrate the potential for mRNA use in gene therapy
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