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Molecular Cell Jan 2022The emergence of CRISPR-Cas systems has accelerated the development of gene editing technologies, which are widely used in the life sciences. To improve the performance... (Review)
Review
The emergence of CRISPR-Cas systems has accelerated the development of gene editing technologies, which are widely used in the life sciences. To improve the performance of these systems, workers have engineered and developed a variety of CRISPR-Cas tools with a broader range of targets, higher efficiency and specificity, and greater precision. Moreover, CRISPR-Cas-related technologies have also been expanded beyond making cuts in DNA by introducing functional elements that permit precise gene modification, control gene expression, make epigenetic changes, and so on. In this review, we introduce and summarize the characteristics and applications of different types of CRISPR-Cas tools. We discuss certain limitations of current approaches and future prospects for optimizing CRISPR-Cas systems.
Topics: Animals; CRISPR-Associated Proteins; CRISPR-Cas Systems; Clustered Regularly Interspaced Short Palindromic Repeats; Diffusion of Innovation; Gene Editing; Humans
PubMed: 34968414
DOI: 10.1016/j.molcel.2021.12.002 -
Molecular Cancer Feb 2022Clustered regularly interspaced short palindromic repeats (CRISPR) system provides adaptive immunity against plasmids and phages in prokaryotes. This system inspires the... (Review)
Review
Clustered regularly interspaced short palindromic repeats (CRISPR) system provides adaptive immunity against plasmids and phages in prokaryotes. This system inspires the development of a powerful genome engineering tool, the CRISPR/CRISPR-associated nuclease 9 (CRISPR/Cas9) genome editing system. Due to its high efficiency and precision, the CRISPR/Cas9 technique has been employed to explore the functions of cancer-related genes, establish tumor-bearing animal models and probe drug targets, vastly increasing our understanding of cancer genomics. Here, we review current status of CRISPR/Cas9 gene editing technology in oncological research. We first explain the basic principles of CRISPR/Cas9 gene editing and introduce several new CRISPR-based gene editing modes. We next detail the rapid progress of CRISPR screening in revealing tumorigenesis, metastasis, and drug resistance mechanisms. In addition, we introduce CRISPR/Cas9 system delivery vectors and finally demonstrate the potential of CRISPR/Cas9 engineering to enhance the effect of adoptive T cell therapy (ACT) and reduce adverse reactions.
Topics: Animals; CRISPR-Cas Systems; Gene Editing; Genomics; Humans; Neoplasms; Oncogenes
PubMed: 35189910
DOI: 10.1186/s12943-022-01518-8 -
Cell Jul 2022In vivo gene editing therapies offer the potential to treat the root causes of many genetic diseases. Realizing the promise of therapeutic in vivo gene editing... (Review)
Review
In vivo gene editing therapies offer the potential to treat the root causes of many genetic diseases. Realizing the promise of therapeutic in vivo gene editing requires the ability to safely and efficiently deliver gene editing agents to relevant organs and tissues in vivo. Here, we review current delivery technologies that have been used to enable therapeutic in vivo gene editing, including viral vectors, lipid nanoparticles, and virus-like particles. Since no single delivery modality is likely to be appropriate for every possible application, we compare the benefits and drawbacks of each method and highlight opportunities for future improvements.
Topics: CRISPR-Cas Systems; Gene Editing; Genetic Therapy; Genetic Vectors; Liposomes; Nanoparticles
PubMed: 35798006
DOI: 10.1016/j.cell.2022.03.045 -
International Journal of Molecular... Dec 2020The discovery of clustered, regularly interspaced short palindromic repeats (CRISPR) and their cooperation with CRISPR-associated (Cas) genes is one of the greatest... (Review)
Review
The discovery of clustered, regularly interspaced short palindromic repeats (CRISPR) and their cooperation with CRISPR-associated (Cas) genes is one of the greatest advances of the century and has marked their application as a powerful genome engineering tool. The CRISPR-Cas system was discovered as a part of the adaptive immune system in bacteria and archaea to defend from plasmids and phages. CRISPR has been found to be an advanced alternative to zinc-finger nucleases (ZFN) and transcription activator-like effector nucleases (TALEN) for gene editing and regulation, as the CRISPR-Cas9 protein remains the same for various gene targets and just a short guide RNA sequence needs to be altered to redirect the site-specific cleavage. Due to its high efficiency and precision, the Cas9 protein derived from the type II CRISPR system has been found to have applications in many fields of science. Although CRISPR-Cas9 allows easy genome editing and has a number of benefits, we should not ignore the important ethical and biosafety issues. Moreover, any tool that has great potential and offers significant capabilities carries a level of risk of being used for non-legal purposes. In this review, we present a brief history and mechanism of the CRISPR-Cas9 system. We also describe on the applications of this technology in gene regulation and genome editing; the treatment of cancer and other diseases; and limitations and concerns of the use of CRISPR-Cas9.
Topics: Animals; CRISPR-Cas Systems; Epigenesis, Genetic; Gene Editing; Genetic Therapy; Humans
PubMed: 33339441
DOI: 10.3390/ijms21249604 -
Transfusion and Apheresis Science :... Feb 2021Sickle cell disease (SCD) is the most common monogenic blood disorder marked by severe pain, end-organ damage, and early mortality. Treatment options for SCD remain very... (Review)
Review
Sickle cell disease (SCD) is the most common monogenic blood disorder marked by severe pain, end-organ damage, and early mortality. Treatment options for SCD remain very limited. There are only four FDA approved drugs to reduce acute complications. The only curative therapy for SCD is hematopoietic stem cell transplantation, typically from a matched, related donor. Ex vivo engineering of autologous hematopoietic stem and progenitor cells followed by transplantation of genetically modified cells potentially provides a permanent cure applicable to all patients regardless of the availability of suitable donors and graft-vs-host disease. In this review, we focus on the use of CRISPR/Cas9 gene-editing for curing SCD, including the curative correction of SCD mutation in β-globin (HBB) and the induction of fetal hemoglobin to reverse sickling. We summarize the major achievements and challenges, aiming to provide a clearer perspective on the potential of gene-editing based approaches in curing SCD.
Topics: Anemia, Sickle Cell; CRISPR-Cas Systems; Gene Editing; Humans
PubMed: 33455878
DOI: 10.1016/j.transci.2021.103060 -
Nature Feb 2020Genome editing, which involves the precise manipulation of cellular DNA sequences to alter cell fates and organism traits, has the potential to both improve our... (Review)
Review
Genome editing, which involves the precise manipulation of cellular DNA sequences to alter cell fates and organism traits, has the potential to both improve our understanding of human genetics and cure genetic disease. Here I discuss the scientific, technical and ethical aspects of using CRISPR (clustered regularly interspaced short palindromic repeats) technology for therapeutic applications in humans, focusing on specific examples that highlight both opportunities and challenges. Genome editing is-or will soon be-in the clinic for several diseases, with more applications under development. The rapid pace of the field demands active efforts to ensure that this breakthrough technology is used responsibly to treat, cure and prevent genetic disease.
Topics: Anemia, Sickle Cell; CRISPR-Cas Systems; Gene Editing; Genome, Human; Germ-Line Mutation; Humans; Muscular Dystrophy, Duchenne; Organ Specificity; Patient Safety; beta-Globins
PubMed: 32051598
DOI: 10.1038/s41586-020-1978-5 -
The Yale Journal of Biology and Medicine Dec 2017The CRISPR-Cas genome editing tools have been adopted rapidly in the research community, and they are quickly finding applications in the commercial sector as well. Lest... (Review)
Review
The CRISPR-Cas genome editing tools have been adopted rapidly in the research community, and they are quickly finding applications in the commercial sector as well. Lest we lose track of the broader context, this Perspective presents a brief review of the history of the genome editing platforms and considers a few current technological issues. It then takes a very limited view into the future of this technology and highlights some of the societal issues that require examination and discussion.
Topics: Animals; CRISPR-Cas Systems; DNA Breaks, Double-Stranded; Food; Gene Drive Technology; Gene Editing; Genetic Therapy; Genome; Humans
PubMed: 29259529
DOI: No ID Found -
Scientific Reports Nov 2022Recent advances in genome editing technologies have redefined our ability to probe and precisely edit the human genome and epigenome in vitro and in vivo More...
Recent advances in genome editing technologies have redefined our ability to probe and precisely edit the human genome and epigenome in vitro and in vivo More specifically, RNA-guided CRISPR/Cas systems have revolutionized the field due to their simplicity in design and adaptability across biological systems. This Collection highlights results in CRISPR/Cas technology that increase the efficiency of precision genome editing, and allow genetic manipulation in model systems traditionally intractable to site-directed gene modification.
Topics: Gene Editing
PubMed: 36443399
DOI: 10.1038/s41598-022-24850-x -
Nature Communications May 2018CRISPR is becoming an indispensable tool in biological research. Once known as the bacterial immune system against invading viruses, the programmable capacity of the... (Review)
Review
CRISPR is becoming an indispensable tool in biological research. Once known as the bacterial immune system against invading viruses, the programmable capacity of the Cas9 enzyme is now revolutionizing diverse fields of medical research, biotechnology, and agriculture. CRISPR-Cas9 is no longer just a gene-editing tool; the application areas of catalytically impaired inactive Cas9, including gene regulation, epigenetic editing, chromatin engineering, and imaging, now exceed the gene-editing functionality of WT Cas9. Here, we will present a brief history of gene-editing tools and describe the wide range of CRISPR-based genome-targeting tools. We will conclude with future directions and the broader impact of CRISPR technologies.
Topics: Animals; CRISPR-Cas Systems; Clustered Regularly Interspaced Short Palindromic Repeats; Gene Editing; History, 20th Century; History, 21st Century; Humans
PubMed: 29765029
DOI: 10.1038/s41467-018-04252-2 -
Cells Jul 2020Gene editing that makes target gene modification in the genome by deletion or addition has revolutionized the era of biomedicine. Clustered regularly interspaced short... (Review)
Review
Gene editing that makes target gene modification in the genome by deletion or addition has revolutionized the era of biomedicine. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 emerged as a substantial tool due to its simplicity in use, less cost and extraordinary efficiency than the conventional gene-editing tools, including zinc finger nucleases (ZFNs) and Transcription activator-like effector nucleases (TALENs). However, potential off-target activities are crucial shortcomings in the CRISPR system. Numerous types of approaches have been developed to reduce off-target effects. Here, we review several latest approaches to reduce the off-target effects, including biased or unbiased off-target detection, cytosine or adenine base editors, prime editing, dCas9, Cas9 paired nickase, ribonucleoprotein (RNP) delivery and truncated gRNAs. This review article provides extensive information to cautiously interpret off-target effects to assist the basic and clinical applications in biomedicine.
Topics: Animals; CRISPR-Associated Protein 9; CRISPR-Cas Systems; DNA Repair; Gene Editing; Humans; RNA, Guide, CRISPR-Cas Systems; Ribonucleoproteins
PubMed: 32630835
DOI: 10.3390/cells9071608