Self-Amplifying RNA Approach for Protein Replacement Therapy

    October 2022 in “ International Journal of Molecular Sciences ”
    Dimitri Papukashvili, Nino Rcheulishvili, Cong Liu, Yang Ji, Yaohua He, Peng George Wang
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    TLDR Self-amplifying RNA could be a better option for protein replacement therapy with lower doses and lasting effects, but delivering it into cells is still challenging.
    The review discusses the potential of self-amplifying RNA (saRNA) for protein replacement therapy in various health disorders, including rare hereditary diseases and single-gene disorders like Alpha-1 Antitrypsin Deficiency (AATD). The saRNA approach is considered more advanced than conventional mRNA therapy due to its lower dosage requirements, fewer side effects, and long-lasting effects. It has been tested preclinically and is undergoing clinical trials. The saRNA approach could also be used for cosmetic purposes, such as treating alopecia by activating certain signaling pathways involved in hair growth. However, the delivery of saRNA to target cells remains a challenge due to its large structure. Various delivery platforms, including nanoparticles and nanoemulsions, are being explored to protect saRNA from degradation and facilitate cellular uptake. Despite some limitations, the advantages of saRNA technology are considered to outweigh the challenges. More preclinical and clinical studies are needed to further explore the potential of saRNA-based therapies for protein replacement.
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