Current Advances in RNA Therapeutics for Human Diseases DOI Open Access
Hannah Zogg, Rajan Singh, Seungil Ro

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2736 - 2736

Published: March 1, 2022

Following the discovery of nucleic acids by Friedrich Miescher in 1868, DNA and RNA were recognized as genetic code containing necessary information for proper cell functioning. In years following these discoveries, vast knowledge seemingly endless roles have become better understood. Additionally, many new types RNAs discovered that seemed to no coding properties (non-coding RNAs), such microRNAs (miRNAs). The created a avenue treating various human diseases. However, is relatively unstable degraded fairly rapidly once administered; this has led development novel delivery mechanisms, nanoparticles increase stability well prevent off-target effects molecules. Current advances RNA-based therapies substantial promise preventing diseases disorders through fixing pathology instead merely symptomology similarly traditional therapeutics. Although therapeutics made it clinical trials, only few been FDA approved thus far. results trials ambivalent date, with some studies demonstrating potent efficacy, whereas others limited effectiveness and/or toxicity. Momentum building clinic therapeutics; future care will likely comprise promising This review focuses on current addresses challenges their development.

Language: Английский

A brave new world of RNA-binding proteins DOI
Matthias W. Hentze, Alfredo Castelló, Thomas Schwarzl

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2018, Volume and Issue: 19(5), P. 327 - 341

Published: Jan. 17, 2018

Language: Английский

Citations

1493
mRNA vaccines for infectious diseases: principles, delivery and clinical translation DOI Open Access
Namit Chaudhary, Drew Weissman, Kathryn A. Whitehead

et al.

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(11), P. 817 - 838

Published: Aug. 25, 2021

Language: Английский

Citations

1005
The Discovery of Ribosome Heterogeneity and Its Implications for Gene Regulation and Organismal Life DOI Creative Commons
Naomi R. Genuth, Maria Barna

Molecular Cell, Journal Year: 2018, Volume and Issue: 71(3), P. 364 - 374

Published: Aug. 1, 2018

Language: Английский

Citations

436
The promise of mRNA vaccines: a biotech and industrial perspective DOI Creative Commons

Nicholas A. C. Jackson,

Kent E. Kester,

Danilo R. Casimiro

et al.

npj Vaccines, Journal Year: 2020, Volume and Issue: 5(1)

Published: Feb. 4, 2020

Abstract mRNA technologies have the potential to transform areas of medicine, including prophylaxis infectious diseases. The advantages for vaccines range from acceleration immunogen discovery rapid response and multiple disease target manufacturing. A greater understanding quality attributes that dictate translation efficiency, as well a comprehensive appreciation importance delivery, are influencing new era investment in development activities. application translational sciences growing early-phase clinical experience continue inform candidate vaccine selection. Here we review state art prevention diseases by using pertinent topics biotechnology pharmaceutical industries.

Language: Английский

Citations

430
Advances in COVID-19 mRNA vaccine development DOI Creative Commons
Enyue Fang, Xiaohui Liu, Miao Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: March 23, 2022

Abstract To date, the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) has determined 399,600,607 cases and 5,757,562 deaths worldwide. COVID-19 is a serious threat to human health globally. The World Health Organization (WHO) declared pandemic major public emergency. Vaccination most effective economical intervention for controlling spread of epidemics, consequently saving lives protecting population. Various techniques have been employed in development vaccines. Among these, messenger RNA (mRNA) vaccine drawing increasing attention owing its great application prospects advantages, which include short cycle, easy industrialization, simple production process, flexibility respond new variants, capacity induce better immune response. This review summarizes current knowledge on structural characteristics, antigen design strategies, delivery systems, industrialization potential, quality control, latest clinical trials real-world data mRNA vaccines as well technology. Current challenges future directions preventive infectious diseases are also discussed.

Language: Английский

Citations

414
Human 5′ UTR design and variant effect prediction from a massively parallel translation assay DOI
Paul Sample, Ban Wang, David W. Reid

et al.

Nature Biotechnology, Journal Year: 2019, Volume and Issue: 37(7), P. 803 - 809

Published: July 1, 2019

Language: Английский

Citations

325
m6A in mRNA coding regions promotes translation via the RNA helicase-containing YTHDC2 DOI Creative Commons
Yuanhui Mao, L. Dong, Xiaomin Liu

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Nov. 25, 2019

Abstract Dynamic mRNA modification in the form of N 6 -methyladenosine (m A) adds considerable richness and sophistication to gene regulation. The m A mark is asymmetrically distributed along mature mRNAs, with approximately 35% residues located within coding region (CDS). It has been suggested that methylation CDS slows down translation elongation. However, neither decoding feature endogenous mRNAs nor physiological significance clearly defined. Here, we found leads ribosome pausing a codon-specific manner. Unexpectedly, removing from these transcripts results further decrease translation. systemic analysis RNA structural datasets revealed positively regulates by resolving secondary structures. We demonstrate elongation-promoting effect requires helicase-containing reader YTHDC2. Our findings established uncovered non-overlapping function proteins.

Language: Английский

Citations

325
mRNA vaccines for COVID-19: what, why and how DOI Creative Commons
Jung Woo Park,

Philip N.P. Lagniton,

Yu Liu

et al.

International Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 17(6), P. 1446 - 1460

Published: Jan. 1, 2021

The Coronavirus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2), has impacted human lives in the most profound ways with millions of infections and deaths.Scientists pharmaceutical companies have been race to produce vaccines against SARS-CoV-2.Vaccine generation usually demands years developing testing for efficacy safety.However, it only took less than one year generate two mRNA from their development deployment.The rapid production time, cost-effectiveness, versatility vaccine design, clinically proven ability induce cellular humoral immune response crowned spotlights as promising candidates fight pandemic.In this review, we discuss general principles design working mechanisms vaccines, provide an up-to-date summary pre-clinical clinical trials on seven anti-COVID-19 candidate focus already licensed vaccination.In addition, highlight key strategies designing maximize expression immunogens avoid intrinsic innate response.We also some perspective future COVID-19 other pathogens.

Language: Английский

Citations

275
Interferons and viruses induce a novel truncated ACE2 isoform and not the full-length SARS-CoV-2 receptor DOI Creative Commons
Olusegun O. Onabajo, Abdul Rouf Banday, Megan L. Stanifer

et al.

Nature Genetics, Journal Year: 2020, Volume and Issue: 52(12), P. 1283 - 1293

Published: Oct. 19, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme (ACE2) for entry into target cells. ACE2 has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in expression levels could be important susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, transcriptionally independent truncated isoform ACE2, designate deltaACE2 (dACE2). We demonstrate that dACE2, but not is ISG. In The Cancer Genome Atlas, dACE2 was enriched squamous tumors respiratory, gastrointestinal and urogenital tracts. vitro, lacks 356 amino-terminal amino acids, non-functional binding SARS-CoV-2 spike protein carboxypeptidase. Our results suggest ISG-type induction IFN-high conditions created by treatments, inflammatory tumor microenvironment viral co-infections unlikely increase cellular promote infection. newly identified unable bind protein. Truncated full-length induced interferons viruses, thus suggesting such are SARS-CoV-2.

Language: Английский

Citations

253
Novel approaches for vaccine development DOI Creative Commons
Makda S. Gebre,

Luis A. Brito,

Lisa H. Tostanoski

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(6), P. 1589 - 1603

Published: March 1, 2021

Language: Английский

Citations

244