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 Latest Advances of Virology Research Using CRISPR/Cas9-Based Gene-Editing Technology and Its Application to Vaccine Development

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 779
Author(s):  
Man Teng ◽  
Yongxiu Yao ◽  
Venugopal Nair ◽  
Jun Luo
Keyword(s):  
Biological Sciences ◽  
Gene Therapy ◽  
Genetic Engineering ◽  
Gene Function ◽  
Viral Genome ◽  
Gene Editing ◽  
Vaccine Development ◽  
Future Prospects ◽  
Dna Viruses ◽  
Viral Genomes

In recent years, the CRISPR/Cas9-based gene-editing techniques have been well developed and applied widely in several aspects of research in the biological sciences, in many species, including humans, animals, plants, and even in viruses. Modification of the viral genome is crucial for revealing gene function, virus pathogenesis, gene therapy, genetic engineering, and vaccine development. Herein, we have provided a brief review of the different technologies for the modification of the viral genomes. Particularly, we have focused on the recently developed CRISPR/Cas9-based gene-editing system, detailing its origin, functional principles, and touching on its latest achievements in virology research and applications in vaccine development, especially in large DNA viruses of humans and animals. Future prospects of CRISPR/Cas9-based gene-editing technology in virology research, including the potential shortcomings, are also discussed.

scholarly journals Reevaluating the Risk of Smallpox Reemergence

2020 ◽  
Vol 185 (7-8) ◽  
pp. e952-e957 ◽  
Author(s):  
C Raina MacIntyre
Keyword(s):  
United States ◽  
Synthetic Biology ◽  
Genetic Engineering ◽  
Gene Editing ◽  
The United States ◽  
Variola Virus ◽  
Preparedness Planning ◽  
High Security ◽  
Bioterrorism Agent ◽  
New Treatments

Abstract Introduction Smallpox, caused by variola virus, was eradicated in 1980, but remains a category A bioterrorism agent. A decade ago, smallpox ranked second after anthrax in a multifactorial risk priority scoring analysis of category A bioterrorism agents. However, advances in genetic engineering and synthetic biology, including published methods for synthesizing an Orthopoxvirus, require the assumptions of this scoring for smallpox and other category A agents to be reviewed. Materials and Methods The risk priority framework was reviewed and revised to account for the capability for creation of synthetic or engineered smallpox and other category A agents. Results The absolute score for all agents increased because of gene editing and synthetic biology capability, which was not present when the framework was developed more than a decade ago, although new treatments revised scores downward for smallpox, Ebola, and botulism. In the original framework, smallpox scored 0 for global availability, given the high security around known seed stocks of variola in two laboratories in the United States and Russia. Now, smallpox can be created using synthetic biology, raising the score for this criterion to 2. Other agents too, such as Ebola, score higher for availability, based on synthetic biology capability. When advances in synthetic biology and genetic engineering are considered, smallpox and anthrax are now equally ranked the highest category A bioterrorism agents for planning and preparedness. Conclusions Revision of a risk priority framework for category A bioterrorism agents shows that smallpox should be elevated in priority for preparedness planning, and that gene editing and synthetic biology raises the overall risk for all agents. The ranking of categories A, B, and C agents should also be revisited, as there is an endless possibility of engineered threats that may be more severe than any agent on the category A list.

scholarly journals PSVIII-26 Gene editing of complex traits

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 259-260
Author(s):  
Ashley Ling ◽  
Romdhane Rekaya
Keyword(s):  
Genetic Engineering ◽  
Complex Traits ◽  
Genetic Architecture ◽  
Quantitative Traits ◽  
Gene Editing ◽  
Genetic Model ◽  
Variable Number ◽  
Production Parameters ◽  
Potential Gain ◽  
Better Than

Abstract Gene editing (GE) is a form of genetic engineering in which DNA is removed, inserted or replaced. For simple monogenic traits, the technology has been successfully implemented to create heritable modifications in animals and plants. The benefits of these niche applications are undeniable. For quantitative traits the benefits of GE are hard to quantify mainly because these traits are not genetic enough (low to moderate heritability) and their genetic architecture is often complex. Because its impact on the gene pool through the introduction of heritable modifications, the potential gain from GE must be evaluated within reasonable production parameters and in comparison, with available tools used in animal selection. A simulation was performed to compare GE with genomic selection (GS) and QTN-assisted selection (QAS) under four experimental factors: 1) heritability (0.1 or 0.4), 2) number of QTN affecting the trait (1000 or 10000) and their effect distribution (Gamma or uniform); 3) Percentage of selected females (100% or 33%); and 4) fixed or variable number of edited QTNs. Three models GS (M1), GS and GE (M2), and GS and QAS (M3) were implemented and compared. When the QTN effects were sampled from a Gamma distribution, all females were selected, and non-segregating QTNs were replaced, M2 clearly outperformed M1 and M3, with superiority ranging from 19 to 61%. Under the same scenario, M3 was 7 to 23% superior to M1. As the complexity of the genetic model increased (10000 QTN; uniform distribution), only one third of the females were selected, and the number of edited QTNs was fixed, the superiority of M2 was significantly reduced. In fact, M2 was only slightly better than M3 (2 to 6%). In all cases, M2 and M3 were better than M1. These results indicate that under realistic scenarios, GE for complex traits might have only limited advantages.

scholarly journals CRISPR-Cas9 System for Plant Genome Editing: Current Approaches and Emerging Developments

Agronomy ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1033 ◽  
Author(s):  
Jake Adolf V. Montecillo ◽  
Luan Luong Chu ◽  
Hanhong Bae
Keyword(s):  
Genetic Engineering ◽  
Genome Editing ◽  
Gene Editing ◽  
Fine Tuning ◽  
Plant Genome ◽  
Detection Methods ◽  
Editing Efficiency ◽  
Targeted Gene Editing ◽  
Transgene Detection ◽  
Selection Of

Targeted genome editing using CRISPR-Cas9 has been widely adopted as a genetic engineering tool in various biological systems. This editing technology has been in the limelight due to its simplicity and versatility compared to other previously known genome editing platforms. Several modifications of this editing system have been established for adoption in a variety of plants, as well as for its improved efficiency and portability, bringing new opportunities for the development of transgene-free improved varieties of economically important crops. This review presents an overview of CRISPR-Cas9 and its application in plant genome editing. A catalog of the current and emerging approaches for the implementation of the system in plants is also presented with details on the existing gaps and limitations. Strategies for the establishment of the CRISPR-Cas9 molecular construct such as the selection of sgRNAs, PAM compatibility, choice of promoters, vector architecture, and multiplexing approaches are emphasized. Progress in the delivery and transgene detection methods, together with optimization approaches for improved on-target efficiency are also detailed in this review. The information laid out here will provide options useful for the effective and efficient exploitation of the system for plant genome editing and will serve as a baseline for further developments of the system. Future combinations and fine-tuning of the known parameters or factors that contribute to the editing efficiency, fidelity, and portability of CRISPR-Cas9 will indeed open avenues for new technological advancements of the system for targeted gene editing in plants.

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 Cannabis sativa: From Therapeutic Uses to Micropropagation and Beyond

Plants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2078
Author(s):  
Tristan K. Adams ◽  
Nqobile A. Masondo ◽  
Pholoso Malatsi ◽  
Nokwanda P. Makunga
Keyword(s):  
Tissue Culture ◽  
Genetic Engineering ◽  
Large Scale ◽  
Gene Editing ◽  
Cannabis Sativa ◽  
Scale Production ◽  
Indirect Organogenesis ◽  
Large Scale Production ◽  
Pharmaceutical Industries

The development of a protocol for the large-scale production of Cannabis and its variants with little to no somaclonal variation or disease for pharmaceutical and for other industrial use has been an emerging area of research. A limited number of protocols have been developed around the world, obtained through a detailed literature search using web-based database searches, e.g., Scopus, Web of Science (WoS) and Google Scholar. This article reviews the advances made in relation to Cannabis tissue culture and micropropagation, such as explant choice and decontamination of explants, direct and indirect organogenesis, rooting, acclimatisation and a few aspects of genetic engineering. Since Cannabis micropropagation systems are fairly new fields, combinations of plant growth regulator experiments are needed to gain insight into the development of direct and indirect organogenesis protocols that are able to undergo the acclimation stage and maintain healthy plants desirable to the Cannabis industry. A post-culture analysis of Cannabis phytochemistry after the acclimatisation stage is lacking in a majority of the reviewed studies, and for in vitro propagation protocols to be accepted by the pharmaceutical industries, phytochemical and possibly pharmacological research need to be undertaken in order to ascertain the integrity of the generated plant material. It is rather difficult to obtain industrially acceptable micropropagation regimes as recalcitrance to the regeneration of in vitro cultured plants remains a major concern and this impedes progress in the application of genetic modification technologies and gene editing tools to be used routinely for the improvement of Cannabis genotypes that are used in various industries globally. In the future, with more reliable plant tissue culture-based propagation that generates true-to-type plants that have known genetic and metabolomic integrity, the use of genetic engineering systems including “omics” technologies such as next-generation sequencing and fast-evolving gene editing tools could be implemented to speed up the identification of novel genes and mechanisms involved in the biosynthesis of Cannabis phytochemicals for large-scale production.

scholarly journals Targeted Therapy in Cardiovascular Disease: A Precision Therapy Era

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengda Xu ◽  
Jiangping Song
Keyword(s):  
Targeted Therapy ◽  
Nucleic Acid ◽  
Small Molecules ◽  
Targeted Therapies ◽  
Gene Editing ◽  
Gene Mutations ◽  
Disease Treatment ◽  
Advantages And Disadvantages ◽  
Therapeutic Drugs ◽  
Precision Therapy

Targeted therapy refers to exploiting the specific therapeutic drugs against the pathogenic molecules (a protein or a gene) or cells. The drug specifically binds to disease-causing molecules or cells without affecting normal tissue, thus enabling personalized and precision treatment. Initially, therapeutic drugs included antibodies and small molecules, (e.g. nucleic acid drugs). With the advancement of the biology technology and immunotherapy, the gene editing and cell editing techniques are utilized for the disease treatment. Currently, targeted therapies applied to treat cardiovascular diseases (CVDs) mainly include protein drugs, gene editing technologies, nucleic acid drugs and cell therapy. Although targeted therapy has demonstrated excellent efficacy in pre-clinical and clinical trials, several limitations need to be recognized and overcome in clinical application, (e.g. off-target events, gene mutations, etc.). This review introduces the mechanisms of different targeted therapies, and mainly describes the targeted therapy applied in the CVDs. Furthermore, we made comparative analysis to clarify the advantages and disadvantages of different targeted therapies. This overview is expected to provide a new concept to the treatment of the CVDs.

scholarly journals CRISPR: A Revolutionary Technique... For Humans?

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Chrissa Barroma
Keyword(s):  
Immune System ◽  
Genetic Engineering ◽  
Gene Editing ◽  
Genomic Sequence ◽  
Somatic Cells ◽  
Clinical Implications ◽  
Human Genetic Engineering

CRISPR/Cas9 is a revolutionary technique that carries the possibility of altering the genomic sequence of an organism. Discovered in a bacterial immune system, CRISPR/Cas9 has been a popular topic of discussion since its first publication in 2012. In this essay, the opposing arguments on the use of CRISPR/Cas9 are discussed, based on the practical uses in human genetic engineering. First, the technique is described along with the comparison of other successful gene editing techniques. Secondly, the ethical and clinical implications are also discussed, and the effects of CRISPR use on human germline and somatic cells. This essay aims to answer whether CRISPR/Cas9 should be used to edit the genome of humans?

scholarly journals Gene editing

2018 ◽  
Vol 64 (1) ◽  
pp. 9-12
Author(s):  
Piotr Węgleński
Keyword(s):  
Genetic Engineering ◽  
Gene Editing ◽  
Social Problems ◽  
Metabolic Diseases ◽  
Genetic Diseases ◽  
Model Organisms ◽  
Wild Type ◽  
Gene Engineering ◽  
Working Out ◽  
Asilomar Conference

Development of the gene engineering techniques has raised worries that they will be used for construction of organism endangering humansand environment. In 1975 at the Asilomar conference, geneticists from many countries decided that genetic engineering brings more benefitsthan threats. In last years a new CRISPR-Cas technique emerged . It allows to make the precise changes in genomes, e.g. to inactivate particulargenes or to replace mutated genes by their wild-type alleles. Inactivation in mice of genes corresponding to those whose mutations causethe genetic diseases in man allows to get model organisms for studying the etiology of given disease and for working out the methods of itscuring. This technique can be applied for repairing genes whose mutations result in metabolic diseases and cancer. Some voices were raisedthat the technique can be potentially used for the “improvement” of man, what would create many ethical and social problems. Geneticists,ethicists and lawyers gathered in 2015 at the Washington conference, discussed these problems and proposed rules for their solving.

scholarly journals Ethics, Patents and Genome Editing: A Critical Assessment of Three Options of Technology Governance

2021 ◽  
Vol 3 ◽  
Author(s):  
Oliver Feeney ◽  
Julian Cockbain ◽  
Sigrid Sterckx
Keyword(s):  
Advisory Committee ◽  
Genome Editing ◽  
Gene Editing ◽  
Democratic Legitimacy ◽  
Private Governance ◽  
Genetic Changes ◽  
Technology Governance ◽  
Advantages And Disadvantages ◽  
Regulatory Approach ◽  
Global Coordination

Current methods of genome editing have been steadily realising the once remote possibilities of making effective and realistic genetic changes to humans, animals and plants. To underpin this, only 6 years passed between Charpentier and Doudna’s 2012 CRISPR-Cas9 paper and the first confirmed (more or less) case of gene-edited humans. While the traditional legislative and regulatory approach of governments and international bodies is evolving, there is still considerable divergence, unevenness and lack of clarity. However, alongside the technical progress, innovation has also been taking place in terms of ethical guidance from the field of patenting. The rise of so-called “ethical licensing” is one such innovation, where patent holders’ control over genome editing techniques, such as CRISPR, creates a form of private governance over possible uses of gene-editing through ethical constraints built into their licensing agreements. While there are some immediately apparent advantages (epistemic, speed, flexibility, global reach, court enforced), this route seems problematic for, at least, three important reasons: 1) lack of democratic legitimacy/procedural justice, 2) voluntariness, wider/global coordination, and sustainability/stability challenges and 3) potential motivational effects/problems. Unless these three concerns are addressed, it is not clear if this route is an improvement on the longer, slower traditional regulatory route (despite the aforementioned problems). Some of these concerns seem potentially addressed by another emerging patent-based approach. Parthasarathy proposes government-driven regulation using the patent system, which, she argues, has more transparency and legitimacy than the ethical licensing approach. This proposal includes the formation of an advisory committee that would guide this government-driven approach in terms of deciding when to exert control over gene editing patents. There seem to be some apparent advantages with this approach (over traditional regulation and over the ethical licensing approach mentioned above—speed and stability being central, as well as increased democratic legitimacy). However, problems also arise—such as a “half-way house” of global democratic legitimacy that may not be legitimate enough whilst still compromising speed of decision-making under the “ethical licensing” approach). This paper seeks to highlight the various advantages and disadvantages of the three main regulatory options—traditional regulation, ethical licensing and Parthasarathy’s approach—before suggesting an important, yet realistically achievable, amendment of TRIPS and an alternative proposal of a WTO ethics advisory committee.

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