Delivery Vehicles for Self-amplifying RNA

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Abstract

Self-amplifying RNA (saRNA) is a next-generation nucleic acid technology that is structurally similar to mRNA, but capable of replicating upon delivery into the cytosol. This amplification results in high protein expression from a relatively low dose of saRNA (~100-fold lower than mRNA). The rapid, cost-effective, cell-free manufacturing, low dosage requirement, and acceptable safety profile have drawn spotlight on saRNA, which has recently entered clinical trials. However, similar to mRNA, saRNA formulations need highly protective and robust delivery vehicles to achieve a therapeutic effect. The delivery systems have an integral role on the therapeutic efficacy of the saRNA including, biodistribution, cellular uptake, protein expression, and immunogenicity. In the last three decades, a broad range of non-viral delivery systems for RNA have been investigated. Herein, we discuss the cutting-edge advancements in saRNA delivery platforms including the variety of delivery approaches that have been used for saRNA formulations to date, and the resulting immunogenicity, biodistribution, cellular uptake, protein expression, and effect of route of administration.

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Bathula, N. V., Popova, P., & Blakney, A. (2022). Delivery Vehicles for Self-amplifying RNA. In RNA Technologies (Vol. 13, pp. 355–370). Springer Science and Business Media Deutschland GmbH. https://doi.org/10.1007/978-3-031-08415-7_16

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