scholarly journals CRISPR for Neuromuscular Disorders: Gene Editing and Beyond

Physiology ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 341-353 ◽  
Author(s):  
Courtney S. Young ◽  
April D. Pyle ◽  
Melissa J. Spencer
Keyword(s):  
Gene Editing ◽  
Neuromuscular Disorders ◽  
Therapeutic Strategies ◽  
Therapeutic Considerations ◽  
Target Effects

This is a review describing advances in CRISPR/Cas-mediated therapies for neuromuscular disorders (NMDs). We explore both CRISPR-mediated editing and dead Cas approaches as potential therapeutic strategies for multiple NMDs. Last, therapeutic considerations, including delivery and off-target effects, are also discussed.

scholarly journals Spatiotemporal control of CRISPR/Cas9 gene editing

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Chenya Zhuo ◽  
Jiabin Zhang ◽  
Jung-Hwan Lee ◽  
Ju Jiao ◽  
Du Cheng ◽  
...  
Keyword(s):  
Genetic Engineering ◽  
Gene Editing ◽  
Genetic Regulation ◽  
Clinical Translation ◽  
Small Molecule Activation ◽  
Simple Design ◽  
Advantages And Disadvantages ◽  
Spatiotemporal Control ◽  
Critical Challenge ◽  
Target Effects

AbstractThe clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) gene editing technology, as a revolutionary breakthrough in genetic engineering, offers a promising platform to improve the treatment of various genetic and infectious diseases because of its simple design and powerful ability to edit different loci simultaneously. However, failure to conduct precise gene editing in specific tissues or cells within a certain time may result in undesirable consequences, such as serious off-target effects, representing a critical challenge for the clinical translation of the technology. Recently, some emerging strategies using genetic regulation, chemical and physical strategies to regulate the activity of CRISPR/Cas9 have shown promising results in the improvement of spatiotemporal controllability. Herein, in this review, we first summarize the latest progress of these advanced strategies involving cell-specific promoters, small-molecule activation and inhibition, bioresponsive delivery carriers, and optical/thermal/ultrasonic/magnetic activation. Next, we highlight the advantages and disadvantages of various strategies and discuss their obstacles and limitations in clinical translation. Finally, we propose viewpoints on directions that can be explored to further improve the spatiotemporal operability of CRISPR/Cas9.

scholarly journals Gene editing using CRISPR-Cas9 for the treatment of lung cancer

2016 ◽  
pp. 178-180 ◽  
Author(s):  
Andres Castillo
Keyword(s):  
Applied Sciences ◽  
Lung Cancer ◽  
High Precision ◽  
Genetic Information ◽  
Gene Editing ◽  
Therapeutic Strategies ◽  
Technological Advance ◽  
Genetic Origin ◽  
New Era ◽  
Health Area

In 2015, the journal Science chose CRISPR-Cas9 technology as the most important technological advance of science in the last years. This magazine announced the beginning of a new era of biotechnology in which it would be possible to edit, correct and modify the genetic information of any cell in a feasible, fast and cheap way; and most importantly, with high precision. Its implementation in research laboratories in basic and applied sciences could help to develop therapeutic strategies for the health area with the main objective of healing diseases with a known genetic origin, and that until now have been impossible to cure

scholarly journals Evading Evasion

2018 ◽  
pp. 25-27
Author(s):  
Mostafa Mohammed Elsabagh
Keyword(s):  
Gene Editing ◽  
Lack Of Control ◽  
Target Effects ◽  
The Way

The CRISPR-Cas9 system has paved the way for realizing gene-editing, but its main weakness lies in its potential for off-target effects. Studies into phages reveal that they express “anti-CRISPR” proteins which if harnessed, could provide us with the solution to this lack of control.

scholarly journals Prime editing for functional repair in patient-derived disease models

2020 ◽  
Author(s):  
Imre F. Schene ◽  
Indi P. Joore ◽  
Rurika Oka ◽  
Michal Mokry ◽  
Anke H.M. van Vugt ◽  
...  
Keyword(s):  
Adult Stem Cells ◽  
Gene Editing ◽  
Therapeutic Potential ◽  
Gene Encoding ◽  
Base Editing ◽  
Homology Directed Repair ◽  
Genome Wide ◽  
Culture Models ◽  
Liver Organoids ◽  
Target Effects

AbstractPrime editing is a novel genome editing technology using fusion proteins of Cas9-nickase and reverse transcriptase, that holds promise to correct the vast majority of genetic defects. We develop prime editing for primary adult stem cells grown in organoid culture models. First, we generate precise in-frame deletions in the gene encoding ß-catenin (CTNNB1) that result in proliferation independent of Wnt-stimuli, mimicking a mechanism of the development of liver cancer. Moreover, prime editing functionally recovers diseasecausing mutations in intestinal organoids from patients with DGAT1-deficiency and liver organoids from a patient with Wilson disease (ATP7B). Prime editing is as efficient in 3D grown organoids as in 2D grown cell lines and offers greater precision than Cas9-mediated homology directed repair (HDR). Base editing remains more reliable than prime editing but is restricted to a subgroup of pathogenic mutations. Whole-genome sequencing of four prime-edited clonal organoid lines reveals absence of genome-wide off-target effects underscoring therapeutic potential of this versatile and precise gene editing strategy.

scholarly journals Prime editing for functional repair in patient-derived disease models

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Imre F. Schene ◽  
Indi P. Joore ◽  
Rurika Oka ◽  
Michal Mokry ◽  
Anke H. M. van Vugt ◽  
...  
Keyword(s):  
Adult Stem Cells ◽  
Gene Editing ◽  
Therapeutic Potential ◽  
Gene Encoding ◽  
Base Editing ◽  
Homology Directed Repair ◽  
Genome Wide ◽  
Culture Models ◽  
Liver Organoids ◽  
Target Effects

Abstract Prime editing is a recent genome editing technology using fusion proteins of Cas9-nickase and reverse transcriptase, that holds promise to correct the vast majority of genetic defects. Here, we develop prime editing for primary adult stem cells grown in organoid culture models. First, we generate precise in-frame deletions in the gene encoding β‐catenin (CTNNB1) that result in proliferation independent of Wnt-stimuli, mimicking a mechanism of the development of liver cancer. Moreover, prime editing functionally recovers disease-causing mutations in intestinal organoids from patients with DGAT1-deficiency and liver organoids from a patient with Wilson disease (ATP7B). Prime editing is as efficient in 3D grown organoids as in 2D grown cell lines and offers greater precision than Cas9-mediated homology directed repair (HDR). Base editing remains more reliable than prime editing but is restricted to a subgroup of pathogenic mutations. Whole-genome sequencing of four prime-edited clonal organoid lines reveals absence of genome-wide off-target effects underscoring therapeutic potential of this versatile and precise gene editing strategy.

scholarly journals Heart Failure and Cognitive Impairment: Clinical Relevance and Therapeutic Considerations

2019 ◽  
Vol 15 (4) ◽  
pp. 291-303 ◽  
Author(s):  
Tuoyo O. Mene-Afejuku ◽  
Monica Pernia ◽  
Uzoma N. Ibebuogu ◽  
Shobhana Chaudhari ◽  
Savi Mushiyev ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cognitive Impairment ◽  
The United States ◽  
Mortality Rates ◽  
Poor Quality ◽  
Therapeutic Strategies ◽  
High Rate ◽  
Common Cause ◽  
Therapeutic Considerations

: Heart failure (HF) is a devastating condition characterized by poor quality of life, numerous complications, high rate of readmission and increased mortality. HF is the most common cause of hospitalization in the United States especially among people over the age of 64 years. The number of people grappling with the ill effects of HF is on the rise as the number of people living to an old age is also on the increase. : Several factors have been attributed to these high readmission and mortality rates among which are; poor adherence with therapy, inability to keep up with clinic appointments and even failure to recognize early symptoms of HF deterioration which may be a result of cognitive impairment. : Therefore, this review seeks to compile the most recent information about the links between HF and dementia or cognitive impairment. We also assessed the prognostic consequences of cognitive impairment complicating HF, therapeutic strategies among patients with HF and focus on future areas of research that would reduce the prevalence of cognitive impairment, reduce its severity and also ameliorate the effect of cognitive impairment coexisting with HF.

scholarly journals crisprSQL: a novel database platform for CRISPR/Cas off-target cleavage assays

2020 ◽  
Vol 49 (D1) ◽  
pp. D855-D861
Author(s):  
Florian Störtz ◽  
Peter Minary
Keyword(s):  
Gene Editing ◽  
Target Prediction ◽  
Current Version ◽  
Therapeutic Gene ◽  
Guide Rnas ◽  
Rodent Cell ◽  
Ongoing Development ◽  
Database Platform ◽  
Target Effects

Abstract With ongoing development of the CRISPR/Cas programmable nuclease system, applications in the area of in vivo therapeutic gene editing are increasingly within reach. However, non-negligible off-target effects remain a major concern for clinical applications. Even though a multitude of off-target cleavage datasets have been published, a comprehensive, transparent overview tool has not yet been established. Here, we present crisprSQL (http://www.crisprsql.com), an interactive and bioinformatically enhanced collection of CRISPR/Cas9 off-target cleavage studies aimed at enriching the fields of cleavage profiling, gene editing safety analysis and transcriptomics. The current version of crisprSQL contains cleavage data from 144 guide RNAs on 25,632 guide-target pairs from human and rodent cell lines, with interaction-specific references to epigenetic markers and gene names. The first curated database of this standard, it promises to enhance safety quantification research, inform experiment design and fuel development of computational off-target prediction algorithms.

A Review: Computational approaches to design sgRNA of CRISPR-Cas9

2021 ◽  
Vol 16 ◽  
Author(s):  
Mohsin Ali Nasir ◽  
Samia Nawaz ◽  
Jia Huang
Keyword(s):  
In Silico ◽  
Gene Editing ◽  
Crucial Point ◽  
Computational Tools ◽  
Computational Approaches ◽  
Guide Rna ◽  
Fast Progression ◽  
Pros And Cons ◽  
Points Of View ◽  
Target Effects

: Clustered regularly interspaced short palindromic repeats along with CRISPR-associated protein mechanisms preserve the memory of previous experiences with DNA invaders, in particular spacers that are embedded in CRISPR arrays between coordinate repeats. There has been a fast progression in the comprehension of this immune system and its implementations; however, there are numerous points of view that anticipate explanations to make the field an energetic research zone. The efficiency of CRISPR-Cas depends on well considered single guide RNA. For this purpose, many bioinformatics methods and tools were created to support the design of greatly active and precise single guide RNA. In-silico single guide RNA architecture is a crucial point for effective gene editing by means of the CRISPR technique. Persistent attempts are prepared to improve in-silico single guide RNA formulation by great on-target effectiveness and decreased off-target effects. This review offers a summary of the CRISPR computational tools to help different researchers to pick a specific tool for their work according to their pros and cons, along with new thoughts to make new computational tools to overcome all existing limitations.

Clustered regularly interspaced short palindromic repeats, a glimpse – impacts in molecular biology, trends and highlights

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Dhivya Selvaraj ◽  
Rajni Dawar ◽  
Pradeep Kumar Sivakumar ◽  
Anita Devi
Keyword(s):  
Molecular Biology ◽  
Infectious Diseases ◽  
Gene Editing ◽  
Inflammatory Diseases ◽  
Genetic Diseases ◽  
Hereditary Diseases ◽  
Hemorrhagic Fevers ◽  
Viral Hemorrhagic Fevers ◽  
Target Effects ◽  
Working Mechanisms

Abstract Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is a novel molecular tool. In recent days, it has been highlighted a lot, as the Nobel prize was awarded for this sector in 2020, and also for its recent use in Covid-19 related diagnostics. Otherwise, it is an eminent gene-editing technique applied in diverse medical zones of therapeutics in genetic diseases, hematological diseases, infectious diseases, etc., research related to molecular biology, cancer, hereditary diseases, immune and inflammatory diseases, etc., diagnostics related to infectious diseases like viral hemorrhagic fevers, Covid-19, etc. In this review, its discovery, working mechanisms, challenges while handling the technique, recent advancements, applications, alternatives have been discussed. It is a cheaper, faster technique revolutionizing the medicinal field right now. However, their off-target effects and difficulties in delivery into the desired cells make CRISPR, not easily utilizable. We conclude that further robust research in this field may promise many interesting, useful results.

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