Evaluation of self-amplifying mRNA platform for protein expression and genetic stability: Implication for mRNA therapies.

Biochem Biophys Res Commun

Gennova Biopharmaceuticals Ltd. ITBT Park, Hinjawadi Phase 2 Road, Hinjawadi Rajiv Gandhi Infotech Park, Hinjawadi, Pune, Maharashtra, 411057, India. Electronic address:

Published: November 2023

AI Article Synopsis

  • The consecutive rollout of mRNA vaccines has sparked discussions about their long-term safety, expression, and potential for integrating into the genome.
  • In this study, researchers evaluated the longevity of antigenic protein expression from self-amplifying mRNA (SAM) vaccines in different cell lines, confirming high levels of protein expression and stability.
  • The results showed no genomic integration of the mRNA and produced promising 3D structures of associated proteins, indicating the potential of the alphavirus-based SAM platform for future vaccine development.

Article Abstract

The consecutive launch of mRNA vaccines like mRNA-1273, BNT 162b2, and GEMCOVAC®-19 against COVID-19 has triggered the debate of long-term expression, safety, and genomic integration of the mRNA vaccine platforms. In the present study, we examined the longevity of antigenic protein expression of mRNA-614 and mRNA-S1LC based on self-amplifying mRNA (SAM) in Expi-293F™, HEK-293 T, and ARPE-19 cells. The protein expression was checked by sandwich-ELISA, FACS, luciferase activity assay, and Western blot. The transcribed antigenic mRNA was sequenced and found to be un-mutated. Additionally, no genomic integration of the reverse transcribed mRNA was observed even up to 7 days post-transfection as verified by PCR. Furthermore, we have generated high-quality 3D structures of non-structural proteins (nsPs) in silico and the genes encoding for the nsPs were cloned and expressed using the T7 system. Findings from the current study have strengthened the fact that the alphavirus-based SAM platform has the potential to become a modality in the upcoming years.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2023.09.016DOI Listing

Publication Analysis

Top Keywords

protein expression
12
self-amplifying mrna
8
genomic integration
8
mrna
7
evaluation self-amplifying
4
mrna platform
4
platform protein
4
expression
4
expression genetic
4
genetic stability
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!