Your browser does not allow saving data (e.g. private mode): bookmarks will be lost when the tab closes.
Search PubMed
Keywords, author, journal, years — results from PubMed, abstracts with Russian translation, bookmarks in your browser.
Found: 26 165
Page 678 of 1000-
Emerging Life Sciences and Possible Threats to International Security.
At the intersection of emerging technologies and international affairs, one of the most provocative areas is the applications of advanced genetic engineering. The COVID-19 global pandemic and uncertainty about the origin of the causative virus illustrates both immediacy and the potential geopolitical implications of such technologies. These new gene editing techniques include one which has garnered a great deal of attention, the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) systems, as well as other, less well-known ones. CRISPR is not the first type of gene editing technology, but it is the most well-known within national and international security debates. Such advancements now allow for easier and more tunable manipulation of the genetic code of life with implications for governance of science and technology and with international security significance in the context of proliferation, deterrence, and unconventional weapons. Biosecurity and other emerging technologies require new models, not simple extrapolations of Cold War or more recent deterrence (or nonproliferation) paradigms.
-
Impacts of oocyte/zygote timing for in vitro fertilization and gene editing in the dog.
Previously, we reported the first live births of dogs using in vitro fertilization (IVF), embryo cryopreservation, and transfer. These techniques have potential applications in the conservation of endangered canids, and development of gene editing/repair technologies that could improve animal welfare by restoring normal gene function and removing predisposition to disease. Here, we used IVF as a springboard for initial attempts at genetic modification through gene editing/repair using the Clustered Regularly-Interspaced Short Palindromic Repeat (CRISPR)-CRISPR-associated endonuclease (Cas9) system. We showed previously that timing is critical for successful IVF in that the canine oocyte must be exposed to the oviductal environment beyond simply reaching metaphase II. Others have shown that timing of injection of CRISPR-Cas9 constructs is critical in gene editing, influencing the extent of genetic mosaicism. Therefore, we investigated whether timing of injection of the gene editing/repair constructs might influence the success of embryo production and gene editing in the dog. We achieved similar IVF success to our prior report in generating 2-cell control embryos, and found equally reduced embryo production whether injection was performed in oocytes prior to fertilization, or in presumptive single-cell zygotes already exposed to sperm. We had no success at generating offspring with precise single-nucleotide changes in KRT71 via homology-directed repair (HDR), but did identify mutation of FGF5 using non-homologous end joining (NHEJ). These findings underscore the difficulties inherent to gene repair, but represent important progress on reproducibility of canine IVF, improved techniques of oocyte/embryo handling, and impact of timing of injections on embryo development.
-
Harnessing the potential of gene editing technology using CRISPR in inflammatory bowel disease.
The molecular scalpel of clustered regularly interspersed short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) technology may be sharp enough to begin cutting the genes implicated in inflammatory bowel disease (IBD) and consequently decrease the 6.3 billion dollar annual financial healthcare burden in the treatment of IBD. For the past few years CRISPR technology has drastically revolutionized DNA engineering and biomedical research field. We are beginning to see its application in gene manipulation of sickle cell disease, human immunodeficiency virus resistant embryologic twin gene modification and IBD genes such as Gatm (Glycine amidinotransferase, mitochondrial), nucleotide-binding oligomerization domain-containing protein 2, KRT12 and other genes implicated in adaptive immune convergence pathways have been subjected to gene editing, however there are very few publications. Furthermore, since Crohn's disease and ulcerative colitis have shared disease susceptibility and share genetic gene profile, it is paramount and is more advantageous to use CRISPR technology to maximize impact. Although, currently CRISPR does have its limitations due to limited number of specific Cas enzymes, off-target activity, protospacer adjacent motifs and crossfire between different target sites. However, these limitations have given researchers further insight on how to augment and manipulate enzymes to enable precise gene excision and limit crossfire between target sites.
-
Nicotine-free, nontransgenic tobacco (Nicotiana tabacum l.) edited by CRISPR-Cas9.
-
CRISPR Technology for Livestock Improvement: Advances and Future Directions.
CRISPR-Cas9 technology is revolutionizing genetic engineering by enabling precise genome modifications across a wide range of organisms, particularly in livestock. This review focuses on livestock improvement and the most recent transformative developments in the application of CRISPR-based genome editing techniques. We analyzed productivity improvements achieved by editing growth factor genes, immunogenic resistance enhancement through the editing of immune loci, and ecological footprint reduction for sustainability. This review also addresses the intricate ethical and regulatory issues posed by the application of CRISPR technology in animal breeding, including concerns about animal welfare violations, unintended off-target effects, and impacts on public perception. Furthermore, we discuss key untapped CRISPR targets in livestock genetics enabled by precision gene editing, the emerging integration of CRISPR with artificial intelligence, and the need for collaboration to address complex ethical and regulatory challenges related to applying CRISPR in animal breeding.
-
Human-mediated outdoor genome editing is not possible so therefore poses no risk to the environment.
There is a world-wide re-examination of the regulations that surround genetic technologies, including gene edited organisms. In many countries, crop plants with small gene edits and where no foreign DNA is introduced are exempt from detailed regulatory assessment. This will allow these types of plants to be released, after assessment for benefit and risk, by plant breeders or plant scientists. The full regulatory risk assessment and risk management of novel (including transgenic) plants is well established and focusses on five key criteria (weediness, gene flow, plant pests, non-target impact, biodiversity). However, plants produced by "traditional" plant breeding technologies, many of which have been subject to random mutagenesis or wide crosses that may introduce enormous numbers of DNA changes, are almost never considered novel so are not assessed for risk through a regulatory system. The most targeted, versatile and widely used gene editing technique involves the enzyme-RNA complex, CRISPR-Cas. This method can produce far more precise and targeted changes than "traditional" mutagenesis techniques. Getting the CRISPR-Cas machinery into plant or animal cells requires highly sterile tissue culture and sophisticated delivery tools. Therefore, gene editing, in the open environment by "field spraying", is not currently possible. While other uses of nucleotide chemistry - such as double stranded RNA - have been applied to plants to knock down gene expression, this is not gene editing and produces no DNA change. Suggestions that gene editing using CRISPR-Cas can occur through spraying directly on to plants in the outside environment is fanciful, incorrect and misleading.
-
Emerging CRISPR Therapies for Precision Gene Editing and Modulation in the Cardiovascular Clinic.
PURPOSE OF REVIEW: Outline the growing suite of novel genome editing tools powered by CRISPR-Cas9 technology that are rapidly advancing towards the clinic for the treatment of cardiovascular disorders. RECENT FINDINGS: A diversity of new genome editors and modulators are being developed for therapies across myriad human diseases. Recent breakthroughs have improved the efficacy, safety, specificity, and delivery of CRISPR-mediated therapies that could impact heart disease in the next decade, though several challenges remain. Many iterations of the original CRISPR system have been developed seeking to leverage its vast therapeutic potential. As examples, nuclease-free editing, precision single-nucleotide editing, gene expression regulation, and epigenomic modifications are now feasible with the current CRISPR-mediated suite of enzymes. These emerging tools will be indispensable for the development of novel cardiovascular therapeutics as demonstrated by recent successes in both basic research laboratories and pre-clinical models. Here, we provide an overview of current and emerging CRISPR-mediated technologies as they pertain to the cardiovascular system, highlighting successful implementations and future challenges.
-
[A modular approach to in vivo gene therapy].
In vivo inactivation of a deleterious gene has been achieved in a small trial, with excellent clinical results. Interestingly, the delivery and editing system is the same as in previous work on a different disease, and the new therapy required simply changing the guide RNA used to target the Cas9 nuclease. This modular approach could be extended to a number of other genetic diseases.
-
CRISPR/Cas9 for Mutagenesis in Rice.
CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9) provides a workhorse for genome editing biotechnology. CRISPR/Cas9 tailored for enabling genome editing has been extensively interrogated and widely utilized for precise genomic alterations in eukaryotic organisms including in plant species. The technology holds the great promise to better understand gene functions, elucidate networks, and improve the performance of crop plants such as increasing grain yields, improving nutritional content, and better combating the biotic and abiotic stresses. Various methods or protocols specific for different plant species have been established. Here, we present a CRISPR/Cas9-mediated genome editing protocol in rice, including detailed information about single-guide RNA design, vector construction, plant transformation, and mutant screening processes.
-
Massively parallel profiling and predictive modeling of the outcomes of CRISPR/Cas9-mediated double-strand break repair.
Non-homologous end-joining (NHEJ) plays an important role in double-strand break (DSB) repair of DNA. Recent studies have shown that the error patterns of NHEJ are strongly biased by sequence context, but these studies were based on relatively few templates. To investigate this more thoroughly, we systematically profiled ∼1.16 million independent mutational events resulting from CRISPR/Cas9-mediated cleavage and NHEJ-mediated DSB repair of 6872 synthetic target sequences, introduced into a human cell line via lentiviral infection. We find that: (i) insertions are dominated by 1 bp events templated by sequence immediately upstream of the cleavage site, (ii) deletions are predominantly associated with microhomology and (iii) targets exhibit variable but reproducible diversity with respect to the number and relative frequency of the mutational outcomes to which they give rise. From these data, we trained a model that uses local sequence context to predict the distribution of mutational outcomes. Exploiting the bias of NHEJ outcomes towards microhomology mediated events, we demonstrate the programming of deletion patterns by introducing microhomology to specific locations in the vicinity of the DSB site. We anticipate that our results will inform investigations of DSB repair mechanisms as well as the design of CRISPR/Cas9 experiments for diverse applications including genome-wide screens, gene therapy, lineage tracing and molecular recording.
PubMed returns only the first 10,000 results — refine the query to see the rest.