CRISPR/Cas9 therapeutics: progress and prospects

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Янв. 16, 2023

Abstract Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing technology is the ideal tool of future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency. A variety efficient Cas9 variants derivatives have been developed to cope complex genomic changes that occur during diseases. However, strategies effectively deliver CRISPR system diseased cells in vivo are currently lacking, nonviral vectors target recognition functions may be focus research. Pathological physiological resulting from disease onset expected serve as identifying factors targeted delivery targets gene editing. Diseases both varied complex, choice appropriate methods different important. Meanwhile, there still many potential challenges identified when targeting CRISPR/Cas9 treatment. This paper reviews current developments three aspects, namely, type, vector, characteristics. Additionally, this summarizes successful examples clinical trials finally describes possible problems associated applications.

Язык: Английский

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Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic

Environmental Research, Год журнала: 2022, Номер 209, С. 112816 - 112816

Опубликована: Янв. 29, 2022

Язык: Английский

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Household Secondary Attack Rates of SARS-CoV-2 by Variant and Vaccination Status

JAMA Network Open, Год журнала: 2022, Номер 5(4), С. e229317 - e229317

Опубликована: Апрель 28, 2022

Importance

An overall household secondary attack rate (SAR) of 18.9% (95% CI, 16.2%-22.0%) through June 17, 2021 was previously reported for SARS-CoV-2. Emerging variants concern and increased vaccination have affected transmission rates.

Objective

To evaluate how SARs changed over time whether varied by viral variant index case contact status.

Data Sources

PubMed medRxiv from 18, 2021, March 8, 2022, reference lists eligible articles. Preprints were included.

Study Selection

Articles with original data reporting the number infected total contacts. Search terms includedSARS-CoV-2,COVID-19,variant,vaccination,secondary rate,secondary infection rate,household,index case, family contacts,close contacts,andfamily transmission. Extraction Synthesis The Preferred Reporting Items Systematic Reviews Meta-Analyses guideline followed. Meta-analyses used generalized linear mixed models to obtain SAR estimates 95% CIs.

Main Outcomes Measures

stratified covariates according variant, status, identification period. estimate vaccine effectiveness on basis probability susceptibility (VES,p), infectiousness given (VEI,p), (VET,p).

Results

Household higher 33 studies midpoints in 2022 (37.3%; 32.7% 42.1%) compared 63 April 2020 (15.5%; 13.2% 18.2%). 42.7% 35.4% 50.4%) Omicron (7 studies), 36.4% 33.4% 39.5%) Alpha (11 29.7% 23.0% 37.3%) Delta (16 22.5% 18.6% 26.8%) Beta (3 studies). For full vaccination,VES,pwas 78.6% 76.0% 80.9%) Alpha, 56.4% 54.6% 58.1%) Delta, 18.1% −18.3% 43.3%) Omicron;VEI,pwas 75.3% 69.9% 79.8%) 21.9% 11.0% 31.5%) 18.2% 0.6% 32.6%) Omicron; andVET,pwas 94.7% 93.3% 95.8%) 64.4% 58.0% 69.8%) 35.8% 13.0% 52.6%) Omicron.

Conclusions Relevance

These results suggest that emerging SARS-CoV-2 transmissibility. Full associated reductions infectiousness, but more so than changes estimated underscore challenges developing effective vaccines concomitant evolution.

Язык: Английский

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Global emerging Omicron variant of SARS-CoV-2: Impacts, challenges and strategies

Journal of Infection and Public Health, Год журнала: 2022, Номер 16(1), С. 4 - 14

Опубликована: Ноя. 19, 2022

Newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuously posing high global public health concerns and panic resulting in waves disease 2019 (COVID-19) pandemic. Depending on the extent genomic variations, mutations adaptation, few gain ability to spread quickly across many countries, acquire higher virulency cause disease, morbidity mortality. These have been implicated lessening efficacy current COVID-19 vaccines immunotherapies break-through viral infections vaccinated individuals recovered patients. Altogether, these could hinder protective herd immunity be achieved through ongoing progressive vaccination. Currently, only variant interest SARS-CoV-2 is Omicron that was first identified South Africa. In this review, we present overview with a special focus variant, its lineages hybrid variants. We discuss hypotheses origin, genetic change underlying molecular mechanism behind transmissibility immune escape variant. Major related including available immunotherapeutics vaccines, transmissibility, severity, mortality discussed. last part, challenges strategies counter amid pandemic presented.

Язык: Английский

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Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine

New England Journal of Medicine, Год журнала: 2022, Номер 386(22), С. 2084 - 2096

Опубликована: Май 4, 2022

Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of original strain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) combined with an adjuvant (Adjuvant System 03 [AS03]) to form candidate vaccine.In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years age) a 1:1 ratio receive two intramuscular injections CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective was determine efficacy preventing symptomatic disease 2019 (Covid-19) beginning least 7 after second injection, analysis performed detection 160 cases.A total 24,141 volunteers participated trial; median age participants 29 years. Covid-19 confirmed by polymerase-chain-reaction assay 165 intention-to-treat population; all viral samples could be sequenced contained variants strain. Vaccine 69.5% (95% confidence interval [CI], 56.7 78.8) against any caused five were identified sequencing. In post hoc analysis, 78.8% CI, 55.8 90.8) moderate-to-severe 74.0% 62.1 82.5) among who seronegative baseline. No cases occurred group, which load for breakthrough lower than group factor more 100. Solicited adverse events mostly mild moderate transient frequent group; local 92.3% 45.5% participants, respectively, systemic 87.3% 65.0%. incidence unsolicited similar groups up each dose (22.7% 20.4%) from day 43 through 201 (4.2% 4.0%).The effective spectrum variants, ranging infection disease. (Funded Medicago; ClinicalTrials.gov number, NCT04636697.).

Язык: Английский

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Association Between Vaccination and Acute Myocardial Infarction and Ischemic Stroke After COVID-19 Infection

JAMA, Год журнала: 2022, Номер 328(9), С. 887 - 887

Опубликована: Июль 22, 2022

Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Influenza

Язык: Английский

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Two Years into the COVID-19 Pandemic: Lessons Learned

ACS Infectious Diseases, Год журнала: 2022, Номер 8(9), С. 1758 - 1814

Опубликована: Авг. 8, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and virulent human-infecting that emerged in late December 2019 Wuhan, China, causing disease called (COVID-19), which has massively impacted global public health caused widespread disruption to daily life. The crisis by COVID-19 mobilized scientists authorities across the world rapidly improve our knowledge about this devastating disease, shedding light on its management control, spawned development of new countermeasures. Here we provide an overview state art gained last years virus COVID-19, including origin natural reservoir hosts, viral etiology, epidemiology, modes transmission, clinical manifestations, pathophysiology, diagnosis, treatment, prevention, emerging variants, vaccines, highlighting important differences from previously known pathogenic coronaviruses. We also discuss selected key discoveries each topic underline gaps for future investigations.

Язык: Английский

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Delta variant (B.1.617.2) of SARS-CoV-2: Mutations, impact, challenges and possible solutions

Human Vaccines & Immunotherapeutics, Год журнала: 2022, Номер 18(5)

Опубликована: Май 4, 2022

Since commencement of COVID-19 pandemic, several SARS-CoV-2 variants have emerged amid containment efforts via vaccination. The Delta variant (B.1.617.2), discovered in October 2020, was designated as a VOC by the WHO on May 11, 2021. enhanced transmissibility has been associated with critical mutations such D614G, L452R, P681R, and T478K S-protein. increased affinity S-protein ACE2 postulated key reason for decreased vaccine efficacy. As per evidence, possesses efficacy compared to other VOCs like Alpha Beta. This led concerns regarding acquisition novel outbreaks vulnerable communities, including vaccinated people. In this mini-review variant, we explained its evolution characteristics, impact spike infectivity immune evasion, measures combat future outbreaks.

Язык: Английский

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A Systematic Review of Coronavirus Disease 2019 Vaccine Efficacy and Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Disease

Open Forum Infectious Diseases, Год журнала: 2022, Номер 9(6)

Опубликована: Апрель 18, 2022

Billions of doses coronavirus disease 2019 (COVID-19) vaccines have been administered globally, dramatically reducing severe acute respiratory syndrome 2 (SARS-CoV-2) incidence and severity in some settings. Many studies suggest provide a high degree protection against infection disease, but precise estimates vary differ design, outcomes measured, dosing regime, location, circulating virus strains. In this study, we conduct systematic review COVID-19 through February 2022. We included efficacy data from Phase 3 clinical trials for 15 undergoing World Health Organization Emergency Use Listing evaluation real-world effectiveness 8 with observational meeting inclusion criteria. Vaccine metrics collected include asymptomatic infection, any symptomatic COVID-19, including hospitalization death, partial or complete vaccination, variants concern Alpha, Beta, Gamma, Delta, Omicron. additionally the epidemiological principles behind design interpretation vaccine studies, important sources heterogeneity.

Язык: Английский

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Assessment of mutations on RBD in the Spike protein of SARS-CoV-2 Alpha, Delta and Omicron variants

Scientific Reports, Год журнала: 2022, Номер 12(1)

Опубликована: Май 20, 2022

The severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2) variant Omicron spread more rapid than the other variants of SARS-CoV-2 virus. Mutations on Spike (S) protein receptor-binding domain (RBD) are critical for antibody resistance and infectivity variants. In this study, we have used accelerated molecular dynamics (aMD) simulations free energy calculations to present a systematic analysis affinity conformational along with interactions that drive binding between RBD human angiotensin-converting enzyme (ACE2) receptor. We evaluate impacts key mutation occur in RBDs ACE2 results show S has stronger evaluation decomposition per residue shows mutations N440K, T478K, Q493R Q498R observed provided stabilization effect interaction ACE2. Overall, demonstrate faster spreading may be correlated uncharged residues positively charged such as Lys Arg positions RBD.

Язык: Английский

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