CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy

Xu, Yuanyuan; Li, Zhanjun

doi:10.1016/j.csbj.2020.08.031

Cited by 156 publications

(118 citation statements)

References 264 publications

(316 reference statements)

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“…Therefore, genome-editing technology would be a promising tool to upregulate AGE-receptor complexes and down-regulate RAGE/TLRs in order to counteract the harmful effects of AGE-proteins in EC [ 167 ]. Due to its high efficacy, good repeatability, simple design and low cost, the CRISPR/Cas9 technology is successfully used to develop innovative organ-specific therapies for better management of diabetic-associated vascular diseases [ 168 ].…”

Section: Promising Therapies To Reduce Ecd In Diabetesmentioning

confidence: 99%

Endothelial Dysfunction in Diabetes Is Aggravated by Glycated Lipoproteins; Novel Molecular Therapies

2020

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Diabetes and its vascular complications affect an increasing number of people. This disease of epidemic proportion nowadays involves abnormalities of large and small blood vessels, all commencing with alterations of the endothelial cell (EC) functions. Cardiovascular diseases are a major cause of death and disability among diabetic patients. In diabetes, EC dysfunction (ECD) is induced by the pathological increase of glucose and by the appearance of advanced glycation end products (AGE) attached to the plasma proteins, including lipoproteins. AGE proteins interact with their specific receptors on EC plasma membrane promoting activation of signaling pathways, resulting in decreased nitric oxide bioavailability, increased intracellular oxidative and inflammatory stress, causing dysfunction and finally apoptosis of EC. Irreversibly glycated lipoproteins (AGE-Lp) were proven to have an important role in accelerating atherosclerosis in diabetes. The aim of the present review is to present up-to-date information connecting hyperglycemia, ECD and two classes of glycated Lp, glycated low-density lipoproteins and glycated high-density lipoproteins, which contribute to the aggravation of diabetes complications. We will highlight the role of dyslipidemia, oxidative and inflammatory stress and epigenetic risk factors, along with the specific mechanisms connecting them, as well as the new promising therapies to alleviate ECD in diabetes.

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Section: Promising Therapies To Reduce Ecd In Diabetesmentioning

confidence: 99%

Endothelial Dysfunction in Diabetes Is Aggravated by Glycated Lipoproteins; Novel Molecular Therapies

2020

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“…Challenges and ethical considerations about the use of CRISPR technology are not just peculiar to CRISPR but common to all gene editing tools previously employed. Experiences and challenges with gene editing raise discussion on delaying the application of the CRISPR-Cas9 in medical applications until well proven and tested using highly supported basic science [ 88 , 89 , 90 , 91 ]. For instance, an example is the emergence of childhood leukemia arising when the viral vector activated a latent human oncogene, as Double Strand Breaks (DSBs) generated by CRISPR-Cas9 often induces apoptosis.…”

Section: Crispr-cas9 and The Future Of Gene Therapymentioning

confidence: 99%

Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders

et al. 2021

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A new approach is adopted to treat primary immunodeficiency disorders, such as the severe combined immunodeficiency (SCID; e.g., adenosine deaminase SCID [ADA-SCID] and IL-2 receptor X-linked severe combined immunodeficiency [SCID-X1]). The success, along with the feasibility of gene therapy, is undeniable when considering the benefits recorded for patients with different classes of diseases or disorders needing treatment, including SCID-X1 and ADA-SCID, within the last two decades. β-Thalassemia and sickle cell anemia are two prominent monogenic blood hemoglobin disorders for which a solution has been sought using gene therapy. For instance, transduced autologous CD34+ HSCs via a self-inactivating (SIN)-Lentivirus (LV) coding for a functional copy of the β-globin gene has become a feasible procedure. adeno-associated virus (AAV) vectors have found application in ocular gene transfer in retinal disease gene therapy (e.g., Leber’s congenital amaurosis type 2), where no prior treatment existed. In neurodegenerative disorders, successes are now reported for cases involving metachromatic leukodystrophy causing severe cognitive and motor damage. Gene therapy for hemophilia also remains a viable option because of the amount of cell types that are capable of synthesizing biologically active FVIII and FIX following gene transfer using AAV vectors in vivo to correct hemophilia B (FIX deficiency), and it is considered an ideal target, as proven in preclinical studies. Recently, the clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 gene-editing tool has taken a center stage in gene therapy research and is reported to be efficient and highly precise. The application of gene therapy to these areas has pushed forward the therapeutic clinical application.

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“…As genomic editing using CRISPR-Cas is less time consuming than TALEN and ZFN, it allowed a scientific group from China to obtain over 17 model lines of rabbits, including models of congenital cataract, ectodermal dysplasia, Duchenne muscular dystrophy (DMD), deafness, X-linked hypophosphatemia (XLH), etc., since 2016 [66].…”

Section: Development Of Animal Modelsmentioning

confidence: 99%

CRISPR-Cas Systems: Prospects for Use in Medicine

2020

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CRISPR-Cas systems, widespread in bacteria and archaea, are mainly responsible for adaptive cellular immunity against exogenous DNA (plasmid and phage). However, the latest research shows their involvement in other functions, such as gene expression regulation, DNA repair and virulence. In recent years, they have undergone intensive research as convenient tools for genomic editing, with Cas9 being the most commonly used nuclease. Gene editing may be of interest in biotechnology, medicine (treatment of inherited disorders, cancer, etc.), and in the development of model systems for various genetic diseases. The dCas9 system, based on a modified Cas9 devoid of nuclease activity, called CRISPRi, is widely used to control gene expression in bacteria for new drug biotargets validation and is also promising for therapy of genetic diseases. In addition to direct use for genomic editing in medicine, CRISPR-Cas can also be used in diagnostics, for microorganisms’ genotyping, controlling the spread of drug resistance, or even directly as “smart” antibiotics. This review focuses on the main applications of CRISPR-Cas in medicine, and challenges and perspectives of these approaches.

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CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy

Cited by 156 publications

References 264 publications

Endothelial Dysfunction in Diabetes Is Aggravated by Glycated Lipoproteins; Novel Molecular Therapies

Endothelial Dysfunction in Diabetes Is Aggravated by Glycated Lipoproteins; Novel Molecular Therapies

Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders

CRISPR-Cas Systems: Prospects for Use in Medicine

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