IL-10 modified mRNA monotherapy prolongs survival after composite facial allografting through the induction of mixed chimerism

Aviña, Ana Elena; Paz, Dante De; Huang, Shucai; Chen, Kuan‐Hung; Chang, Yun-Ching; Lee, Chin-Ming; Lin, Chia-Hsien; Wei, Fu‐Chan; Wang, Aline Yen Ling

doi:10.1016/j.omtn.2023.02.016

Cited by 5 publications

(1 citation statement)

References 86 publications

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“…Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has invaded the world, which has promoted the generation of modRNA-based vaccines such as Moderna 1273 with N1-methyl-pseudouridine modification and Pfizer/BNT 162b2 with proline mutation against the COVID-19 pandemic 39 . In addition, interleukin (IL)-10 modRNA has been used to directly produce the anti-inflammatory IL-10 protein in vivo, resulting in prolonged survival of facial allografts through the induction of mixed chimerism 40 . The modRNA for this application included modifications such as m5C, ΨU, a 5′-UTR containing the Kozak sequence, 3′ UTR, poly-A tail, and ARCA.…”

Section: Modified Mrnamentioning

confidence: 99%

Potential Application of Modified mRNA in Cardiac Regeneration

Wang,

Chang,

Chen

et al. 2024

Cell Transplant

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Heart failure remains the leading cause of human death worldwide. After a heart attack, the formation of scar tissue due to the massive death of cardiomyocytes leads to heart failure and sudden death in most cases. In addition, the regenerative ability of the adult heart is limited after injury, partly due to cell-cycle arrest in cardiomyocytes. In the current post-COVID-19 era, urgently authorized modified mRNA (modRNA) vaccines have been widely used to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, modRNA-based protein replacement may act as an alternative strategy for improving heart disease. It is a safe, effective, transient, low-immunogenic, and integration-free strategy for in vivo protein expression, in addition to recombinant protein and stem-cell regenerative therapies. In this review, we provide a summary of various cardiac factors that have been utilized with the modRNA method to enhance cardiovascular regeneration, cardiomyocyte proliferation, fibrosis inhibition, and apoptosis inhibition. We further discuss other cardiac factors, modRNA delivery methods, and injection methods using the modRNA approach to explore their application potential in heart disease. Factors for promoting cardiomyocyte proliferation such as a cocktail of three genes comprising FoxM1, Id1, and Jnk3-shRNA (FIJs), gp130, and melatonin have potential to be applied in the modRNA approach. We also discuss the current challenges with respect to modRNA-based cardiac regenerative medicine that need to be overcome to apply this approach to heart disease. This review provides a short description for investigators interested in the development of alternative cardiac regenerative medicines using the modRNA platform.

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Section: Modified Mrnamentioning

confidence: 99%

Potential Application of Modified mRNA in Cardiac Regeneration

Wang,

Chang,

Chen

et al. 2024

Cell Transplant

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Ex vivo Delivery of Recombinant IL-10 to Human Donor Lungs

Yeung,

Koike,

Wagnetz

et al. 2024

JHLT Open

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Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications

Shi,

Wang

et al. 2024

Sig Transduct Target Ther

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In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge in interest can be largely attributed to the demonstration of distinct advantages offered by various mRNA molecules, alongside the rapid advancements in nucleic acid delivery systems. It is noteworthy that the immunogenicity of mRNA drugs presents a double-edged sword. In the context of immunotherapy, extra supplementation of adjuvant is generally required for induction of robust immune responses. Conversely, in non-immunotherapeutic scenarios, immune activation is unwanted considering the host tolerability and high expression demand for mRNA-encoded functional proteins. Herein, mainly focused on the linear non-replicating mRNA, we overview the preclinical and clinical progress and prospects of mRNA medicines encompassing vaccines and other therapeutics. We also highlight the importance of focusing on the host-specific variations, including age, gender, pathological condition, and concurrent medication of individual patient, for maximized efficacy and safety upon mRNA administration. Furthermore, we deliberate on the potential challenges that mRNA drugs may encounter in the realm of disease treatment, the current endeavors of improvement, as well as the application prospects for future advancements. Overall, this review aims to present a comprehensive understanding of mRNA-based therapies while illuminating the prospective development and clinical application of mRNA drugs.

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IL-10 modified mRNA monotherapy prolongs survival after composite facial allografting through the induction of mixed chimerism

Cited by 5 publications

References 86 publications

Potential Application of Modified mRNA in Cardiac Regeneration

Potential Application of Modified mRNA in Cardiac Regeneration

Ex vivo Delivery of Recombinant IL-10 to Human Donor Lungs

Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications

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