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

Deo, Swarda; Desai, Kaushik; Patare, Aishwarya; Wadapurkar, Rucha; Rade, Saniya; Mahudkar, Siddhi; Sathe, Madhura; Srivastava, Shalini; Prasanna, Pragya; Singh, Ajay

doi:10.1016/j.bbrc.2023.09.016

Cited by 5 publications

(3 citation statements)

References 52 publications

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“…GEMCOVAC-OM consists of an in vitro transcribed mRNA encoding for the spike protein of the Omicron variant of the SARS-CoV-2 virus and cationic lipid nano-emulsion in a buffer containing 10% sucrose in 10 mM sodium citrate, pH 6.5 (ref. 45 ). The complete antigenic sequence that was used has been published in the DDBJ database (accession no.…”

Section: Methodsmentioning

confidence: 99%

An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial

Saraf,

Gurjar,

Kaviraj

et al. 2024

Nat Med

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Here we conducted a multicenter open-label, randomized phase 2 and 3 study to assess the safety and immunogenicity of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-specific (BA.1/B.1.1.529), monovalent, thermostable, self-amplifying mRNA vaccine, GEMCOVAC-OM, when administered intradermally as a booster in healthy adults who had received two doses of BBV152 or ChAdOx1 nCoV-19. GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3. In phase 2, the safety and immunogenicity of GEMCOVAC-OM was compared with our prototype mRNA vaccine GEMCOVAC-19 (D614G variant-specific) in 140 participants. At day 29 after vaccination, there was a significant rise in anti-spike (BA.1) IgG antibodies with GEMCOVAC-OM (P < 0.0001) and GEMCOVAC-19 (P < 0.0001). However, the IgG titers (primary endpoint) and seroconversion were higher with GEMCOVAC-OM (P < 0.0001). In phase 3, GEMCOVAC-OM was compared with ChAdOx1 nCoV-19 in 3,140 participants (safety cohort), which included an immunogenicity cohort of 420 participants. At day 29, neutralizing antibody titers against the BA.1 variant of SARS-CoV-2 were significantly higher than baseline in the GEMCOVAC-OM arm (P < 0.0001), but not in the ChAdOx1 nCoV-19 arm (P = 0.1490). GEMCOVAC-OM was noninferior (primary endpoint) and superior to ChAdOx1 nCoV-19 in terms of neutralizing antibody titers and seroconversion rate (lower bound 95% confidence interval of least square geometric mean ratio >1 and difference in seroconversion >0% for superiority). At day 29, anti-spike IgG antibodies and seroconversion (secondary endpoints) were significantly higher with GEMCOVAC-OM (P < 0.0001). These results demonstrate that GEMCOVAC-OM is safe and boosts immune responses against the B.1.1.529 variant. Clinical Trial Registry India identifier: CTRI/2022/10/046475.

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Section: Methodsmentioning

confidence: 99%

An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial

Saraf,

Gurjar,

Kaviraj

et al. 2024

Nat Med

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“…SAM vaccines directed against SARS-CoV-2 exhibited limited reactogenicity during clinical trials. This method may ultimately prove more potent and cost-efficient when compared to non-replicating mRNA (NRM) vaccines [33].…”

Section: Ivt-mrna: a Comprehensive Exploration Of The Technologymentioning

confidence: 99%

Recruiting In Vitro Transcribed mRNA against Cancer Immunotherapy: A Contemporary Appraisal of the Current Landscape

Miliotou,

Georgiou-Siafis,

Ntenti

et al. 2023

CIMB

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Over 100 innovative in vitro transcribed (IVT)-mRNAs are presently undergoing clinical trials, with a projected substantial impact on the pharmaceutical market in the near future. Τhe idea behind this is that after the successful cellular internalization of IVT-mRNAs, they are subsequently translated into proteins with therapeutic or prophylactic relevance. Simultaneously, cancer immunotherapy employs diverse strategies to mobilize the immune system in the battle against cancer. Therefore, in this review, the fundamental principles of IVT-mRNA to its recruitment in cancer immunotherapy, are discussed and analyzed. More specifically, this review paper focuses on the development of mRNA vaccines, the exploitation of neoantigens, as well as Chimeric Antigen Receptor (CAR) T-Cells, showcasing their clinical applications and the ongoing trials for the development of next-generation immunotherapeutics. Furthermore, this study investigates the synergistic potential of combining the CAR immunotherapy and the IVT-mRNAs by introducing our research group novel, patented delivery method that utilizes the Protein Transduction Domain (PTD) technology to transduce the IVT-mRNAs encoding the CAR of interest into the Natural Killer (NK)-92 cells, highlighting the potential for enhancing the CAR NK cell potency, efficiency, and bioenergetics. While IVT-mRNA technology brings exciting progress to cancer immunotherapy, several challenges and limitations must be acknowledged, such as safety, toxicity, and delivery issues. This comprehensive exploration of IVT-mRNA technology, in line with its applications in cancer therapeutics, offers valuable insights into the opportunities and challenges in the evolving landscape of cancer immunotherapy, setting the stage for future advancements in the field.

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“…mRNA platform is a disease agonist platform where its potential can be harnessed for most of the modalities like vaccines, cell/gene therapy, and protein replacement therapy across various disease indications. mRNA vaccines launched like mRNA-1273, BNT 162b2, Gemcovac®-19, Gemcovac®-OM, and ARCT-154 against COVID-19 have extensively explored the non-amplifying mRNA (NAM) and self-amplifying mRNA (SAM) platforms [ 1 ]. COVID-19, a disease caused by the SARS-CoV-2 virus spread in late 2019 and arose as an emergency that halted the entire world.…”

Section: Introductionmentioning

confidence: 99%

Combinative workflow for mRNA vaccine development

Khanzode,

Soni,

Srivastava

et al. 2024

Biochemistry and Biophysics Reports

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

Cited by 5 publications

References 52 publications

An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial

An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial

Recruiting In Vitro Transcribed mRNA against Cancer Immunotherapy: A Contemporary Appraisal of the Current Landscape

Combinative workflow for mRNA vaccine development

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