CRISPR technology in human diseases

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Abstract

Gene editing is a growing gene engineering technique that allows accurate editing of a broad spectrum of gene‐regulated diseases to achieve curative treatment and also has the potential to be used as an adjunct to the conventional treatment of diseases. Gene editing technology, mainly based on clustered regularly interspaced palindromic repeats (CRISPR)–CRISPR‐associated protein systems, which is capable of generating genetic modifications in somatic cells, provides a promising new strategy for gene therapy for a wide range of human diseases. Currently, gene editing technology shows great application prospects in a variety of human diseases, not only in therapeutic potential but also in the construction of animal models of human diseases. This paper describes the application of gene editing technology in hematological diseases, solid tumors, immune disorders, ophthalmological diseases, and metabolic diseases; focuses on the therapeutic strategies of gene editing technology in sickle cell disease; provides an overview of the role of gene editing technology in the construction of animal models of human diseases; and discusses the limitations of gene editing technology in the treatment of diseases, which is intended to provide an important reference for the applications of gene editing technology in the human disease.

Abstract

Gene editing is an evolving genetic engineering technology that shows great promise for application in a wide range of human diseases, not only for its therapeutic potential, but also for the construction of animal models of human diseases. This review paper describes the application of gene editing technology in hematological disorders, solid tumors, immune disorders, ophthalmic disorders, and metabolic disorders; highlights the therapeutic strategy of gene editing technology in sickle cell disease; outlines the role of gene editing technology in constructing animal models of human diseases; and discusses the limitations of gene editing technology in the treatment of diseases.

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Highly accurate protein structure prediction with AlphaFold

John Jumper, Richard Evans, Alexander Pritzel … (2021)

Proteins are essential to life, and understanding their structure can facilitate a mechanistic understanding of their function. Through an enormous experimental effort 1 – 4 , the structures of around 100,000 unique proteins have been determined 5 , but this represents a small fraction of the billions of known protein sequences 6 , 7 . Structural coverage is bottlenecked by the months to years of painstaking effort required to determine a single protein structure. Accurate computational approaches are needed to address this gap and to enable large-scale structural bioinformatics. Predicting the three-dimensional structure that a protein will adopt based solely on its amino acid sequence—the structure prediction component of the ‘protein folding problem’ 8 —has been an important open research problem for more than 50 years 9 . Despite recent progress 10 – 14 , existing methods fall far short of atomic accuracy, especially when no homologous structure is available. Here we provide the first computational method that can regularly predict protein structures with atomic accuracy even in cases in which no similar structure is known. We validated an entirely redesigned version of our neural network-based model, AlphaFold, in the challenging 14th Critical Assessment of protein Structure Prediction (CASP14) 15 , demonstrating accuracy competitive with experimental structures in a majority of cases and greatly outperforming other methods. Underpinning the latest version of AlphaFold is a novel machine learning approach that incorporates physical and biological knowledge about protein structure, leveraging multi-sequence alignments, into the design of the deep learning algorithm. AlphaFold predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture.

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Lindsey Baden, Hana El Sahly, Brandon Essink … (2020)

Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)

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Author and article information

Contributors

Tianjia Liu: ltj@bcmc.edu.cn

Dongxu Wang: wang_dong_xu@jlu.edu.cn

Journal

Journal ID (nlm-ta): MedComm (2020)

Journal ID (iso-abbrev): MedComm (2020)

Journal ID (doi): 10.1002/(ISSN)2688-2663

Journal ID (publisher-id): MCO2

Title: MedComm

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2688-2663

Publication date (Electronic): 29 July 2024

Publication date Collection: August 2024

Volume: 5

Issue: 8 ( doiID: 10.1002/mco2.v5.8 )

Electronic Location Identifier: e672

Affiliations

[ ¹ ] Laboratory Animal Center College of Animal Science Jilin University Changchun China

[ ² ] Research and Development Centre Baicheng Medical College Baicheng China

[ ³ ] School of Grain Science and Technology Jilin Business and Technology College Changchun China

[ ⁴ ] Department of Hand and Foot Surgery The First Hospital of Jilin University Changchun China

Author notes

[*] [* ] Correspondence

Dongxu Wang, Laboratory Animal Center, College of Animal Science, Jilin University, Changchun, China.

Email: wang_dong_xu@ 123456jlu.edu.cn

Tianjia Liu, Research and Development Centre, Baicheng Medical College, Baicheng, China.

Email: ltj@ 123456bcmc.edu.cn

[#]

These authors contributed equally to this work.

Article

Publisher ID: MCO2672

DOI: 10.1002/mco2.672

PMC ID: 11286548

PubMed ID: 39081515

SO-VID: 62023513-d34e-4f02-9466-1e53a59f90cc

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date revision received : 01 July 2024

Date received : 09 July 2023

Date accepted : 01 July 2024

Page count

Figures: 5, Tables: 6, Pages: 71, Words: 38528

Funding

Funded by: Jilin Province University Key Laboratory Scientific Research Program

Award ID: [2019] No. 004

Funded by: Jilin Education Department Program

Award ID: JJKH20230259KJ

Funded by: Jilin Province Development and Reform Commission Program

Award ID: 2023C028‐6

Funded by: Jilin Scientific and Technological Development Program , doi 10.13039/501100013061;

Award ID: 20210101010JC

Award ID: 20210203080SF

Award ID: 20220505033ZP

Funded by: Wenzhou Science & Technology Bureau Basic Public Welfare Research Project

Award ID: Y20240006

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cover-date August 2024

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.6 mode:remove_FC converted:29.07.2024

Keywords: clinical research,crispr–cas9,gene editing technology,gene therapy,human diseases,sickle cell disease

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Keywords: clinical research, crispr–cas9, gene editing technology, gene therapy, human diseases, sickle cell disease

CRISPR technology in human diseases

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CRISPR/Cas9 editing in human blood

Most cited references 498

Highly accurate protein structure prediction with AlphaFold

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

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