BIOMAT Database Logo BIOMAT Database Logo

CRISPR-derived genome editing therapies: Progress from bench to bedside. 2021

Holly A Rees, and Alex C Minella, and Cameron A Burnett, and Alexis C Komor, and Nicole M Gaudelli
Beam Therapeutics, Cambridge, MA, USA.

The development of CRISPR-derived genome editing technologies has enabled the precise manipulation of DNA sequences within the human genome. In this review, we discuss the initial development and cellular mechanism of action of CRISPR nucleases and DNA base editors. We then describe factors that must be taken into consideration when developing these tools into therapeutic agents, including the potential for unintended and off-target edits when using these genome editing tools, and methods to characterize these types of edits. We finish by considering specific challenges associated with bringing a CRISPR-based therapy to the clinic, including manufacturing, regulatory oversight, and considerations for clinical trials that involve genome editing agents.

UI MeSH Term Description Entries
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D005818 Genetic Engineering Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. Genetic Intervention,Engineering, Genetic,Intervention, Genetic,Genetic Interventions,Interventions, Genetic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072669 Gene Editing Genetic engineering or molecular biology techniques that involve DNA REPAIR mechanisms for incorporating site-specific modifications into a cell's genome. Base Editing,Genome Editing,Editing, Base,Editing, Gene,Editing, Genome
D000076987 CRISPR-Associated Protein 9 An RNA-guided endodeoxyribonuclease that associates with CRISPR SEQUENCES in STREPTOCOCCUS PYOGENES and other bacteria where it participates in an adaptive immune function to cleave foreign DNA complimentary to small GUIDE RNA (sgRNAs). Structurally, Cas9 consists of an ALPHA-HELIX module and a nuclease module connected by a single helix. The nuclease module contains two enzymatic domains: RuvC, which cleaves non-target DNA strand, and an HNH nuclease domain, which cleaves the target strand. Specificity for the DNA target depends on the presence of a protospacer adjacent motif (PAM) sequence, a 2-6 nucleotide DNA sequence immediately following the sequence targeted by Cas9. Cas9 Endonuclease,Cas9 Enzyme,Cas9 Protein,CRISPR Associated Protein 9,Endonuclease, Cas9,Enzyme, Cas9
D000094704 RNA, Guide, CRISPR-Cas Systems A component of CRISPR-Cas SYSTEMS. Cas endodeoxyribonucleases assemble with a guide RNA complex, a hybrid of CRISPR RNA (crRNA) and transactivating crRNA (tracrRNA) molecules, to form an active complex that cleaves DNA. crRNA and tracrRNA can be synthetically fused into a single RNA molecule, namely single guide RNA. Synthetic sgRNA is used with CRISPR-Cas SYSTEMS for targeted GENE EDITING. CRISPR Guide RNA,CRISPR-Cas Systems sgRNA (Single Guide RNA),Guide RNA (CRISPR-Cas Systems),Guide RNA, CRISPR-Cas Systems,RNA, CRISPR Guide,RNA, Guide (CRISPR-Cas Systems),RNA, Single Guide,RNA, Single-Guide,Single Guide RNA,Single-Guide RNA,Transactivating crRNA,crRNA,crRNA, Transactivating,sgRNA (CRISPR-Cas Systems),sgRNA (Single-Guide RNA),tracrRNA,Guide RNA, CRISPR,Guide RNA, CRISPR Cas Systems,Guide RNA, Single
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015316 Genetic Therapy Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions. Gene Therapy,Somatic Gene Therapy,DNA Therapy,Gene Therapy, Somatic,Genetic Therapy, Gametic,Genetic Therapy, Somatic,Therapy, DNA,Therapy, Gene,Therapy, Somatic Gene,Gametic Genetic Therapies,Gametic Genetic Therapy,Genetic Therapies,Genetic Therapies, Gametic,Genetic Therapies, Somatic,Somatic Genetic Therapies,Somatic Genetic Therapy,Therapies, Gametic Genetic,Therapies, Genetic,Therapies, Somatic Genetic,Therapy, Gametic Genetic,Therapy, Genetic,Therapy, Somatic Genetic
D057170 Translational Research, Biomedical The endeavour to traverse a specific step of the translation process of turning an observation in the laboratory, clinic, or community into an intervention that will improve the health of individuals and the public. (from Nat Rev Drug Discov. 2018 July ; 17(7): 455–456.) Translational Medical Research,Translational Research,Translational Research, Medical,Biomedical Translational Research,Medical Research, Translational,Medical Translational Research,Research, Biomedical Translational,Research, Medical Translational,Research, Translational,Research, Translational Medical
D059767 Recombinational DNA Repair Repair of DNA DAMAGE by exchange of DNA between matching sequences, usually between the allelic DNA (ALLELES) of sister chromatids. Homologous Recombination DNA Repair,Homologous Recombination Repair of DNA,Homology-Directed dsDNA Break Repair,Homologous Recombination Double-Stranded Break DNA Repair,Homologous Recombination Repair,Homologous Recombinational Repair,Recombination Repair,Recombinational Repair of DNA,DNA Recombinational Repair,DNA Repair, Recombinational,Homologous Recombination Double Stranded Break DNA Repair,Homologous Recombinational Repairs,Homology Directed dsDNA Break Repair,Recombination Repair, Homologous,Recombinational Repair, Homologous,Repair, Homologous Recombinational,Repair, Recombination,Repair, Recombinational DNA

Related Publications

Holly A Rees, and Alex C Minella, and Cameron A Burnett, and Alexis C Komor, and Nicole M Gaudelli
Genome editing: the road of CRISPR/Cas9 from bench to clinic.
October 2016, Experimental & molecular medicine,
Holly A Rees, and Alex C Minella, and Cameron A Burnett, and Alexis C Komor, and Nicole M Gaudelli
CDG Therapies: From Bench to Bedside.
April 2018, International journal of molecular sciences,
Holly A Rees, and Alex C Minella, and Cameron A Burnett, and Alexis C Komor, and Nicole M Gaudelli
Editorial: CRISPR Medicine: From Bench to Bedside.
January 2017, Current gene therapy,
Holly A Rees, and Alex C Minella, and Cameron A Burnett, and Alexis C Komor, and Nicole M Gaudelli
From Bench to Bed: The Current Genome Editing Therapies for Glaucoma.
January 2022, Frontiers in cell and developmental biology,
Holly A Rees, and Alex C Minella, and Cameron A Burnett, and Alexis C Komor, and Nicole M Gaudelli
From bedside to bench: reverse engineering medical progress.
October 2012, Digestive diseases and sciences,
Holly A Rees, and Alex C Minella, and Cameron A Burnett, and Alexis C Komor, and Nicole M Gaudelli
[Regulatory framework of innovative therapies : From bench to bedside].
July 2011, Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz,
Holly A Rees, and Alex C Minella, and Cameron A Burnett, and Alexis C Komor, and Nicole M Gaudelli
Emerging therapies for Parkinson's disease: from bench to bedside.
November 2014, Pharmacology & therapeutics,
Holly A Rees, and Alex C Minella, and Cameron A Burnett, and Alexis C Komor, and Nicole M Gaudelli
Current Progress of Mitochondrial Genome Editing by CRISPR.
January 2022, Frontiers in physiology,
Holly A Rees, and Alex C Minella, and Cameron A Burnett, and Alexis C Komor, and Nicole M Gaudelli
From bacterial battles to CRISPR crops; progress towards agricultural applications of genome editing.
November 2019, Emerging topics in life sciences,
Holly A Rees, and Alex C Minella, and Cameron A Burnett, and Alexis C Komor, and Nicole M Gaudelli
Progress in Tumor-Associated Macrophages: From Bench to Bedside.
February 2019, Advanced biosystems,
Copied contents to your clipboard!