Браузер не даёт сохранять данные (например, приватный режим): закладки пропадут после закрытия вкладки.
Поиск статей PubMed
Ключевые слова, автор, журнал, годы — результаты из PubMed, аннотации с переводом на русский, закладки в браузере.
Найдено: 26 182
Страница 968 из 1000-
Genetic Editing and Pharmacogenetics in Current And Future Therapy Of Neurocognitive Disorders.
Dementia is an important issue in western societies, and in the following years, this problem will also rise in the developing regions, such as Africa and Asia. The most common types of dementia in adults are Alzheimer's Disease (AD), Dementia with Lewy Bodies (DLB), Frontotemporal Dementia (FTD) and Vascular Dementia (VaD), of which, AD accounts for more than half of the cases. The most prominent symptom of AD is cognitive impairment, currently treated with four drugs: Donepezil, rivastigmine, and galantamine, enhancing cholinergic transmission; as well as memantine, protecting neurons against glutamate excitotoxicity. Despite ongoing efforts, no new drugs in the treatment of AD have been registered for the last ten years, thus multiple studies have been conducted on genetic factors affecting the efficacy of antidementia pharmacotherapy. The researchers investigate the effects of variants in multiple genes, such as ABCB1, ACE, CHAT, CHRNA7, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, CYP3A7, NR1I2, NR1I3, POR, PPAR, RXR, SLC22A1/2/5, SLC47A1, UGT1A6, UGT1A9 and UGT2B7, associated with numerous pathways: the development of pathological proteins, formation and metabolism of acetylcholine, transport, metabolism and excretion of antidementia drugs and transcription factors regulating the expression of genes responsible for metabolism and transport of drugs. The most promising results have been demonstrated for APOE E4, dementia risk variant, BCHE-K, reduced butyrylcholinesterase activity variant, and CYP2D6 UM, ultrarapid hepatic metabolism. Further studies investigate the possibilities of the development of emerging drugs or genetic editing by CRISPR/Cas9 for causative treatment. In conclusion, the pharmacogenetic studies on dementia diseases may improve the efficacy of pharmacotherapy in some patients with beneficial genetic variants, at the same time, identifying the carriers of unfavorable alleles, the potential group of novel approaches to the treatment and prevention of dementia.
-
Cas9-PF, an early flowering and visual selection marker system, enhances the frequency of editing event occurrence and expedites the isolation of genome-edited and transgene-free plants.
-
Use of GRF-GIF chimeras and a ternary vector system to improve maize (Zea mays L.) transformation frequency.
Maize (Zea mays L.) is an important crop that has been widely studied for its agronomic and industrial applications and is one of the main classical model organisms for genetic research. Agrobacterium-mediated transformation of immature maize embryos is a commonly used method to introduce transgenes, but a low transformation frequency remains a bottleneck for many gene-editing applications. Previous approaches to enhance transformation included the improvement of tissue culture media and the use of morphogenic regulators such as BABY BOOM and WUSCHEL2. Here, we show that the frequency can be increased using a pVS1-VIR2 virulence helper plasmid to improve T-DNA delivery, and/or expressing a fusion protein between a GROWTH-REGULATING FACTOR (GRF) and GRF-INTERACTING FACTOR (GIF) protein to improve regeneration. Using hygromycin as a selection agent to avoid escapes, the transformation frequency in the maize inbred line B104 significantly improved from 2.3 to 8.1% when using the pVS1-VIR2 helper vector with no effect on event quality regarding T-DNA copy number. Combined with a novel fusion protein between ZmGRF1 and ZmGIF1, transformation frequencies further improved another 3.5- to 6.5-fold with no obvious impact on plant growth, while simultaneously allowing efficient CRISPR-/Cas9-mediated gene editing. Our results demonstrate how a GRF-GIF chimera in conjunction with a ternary vector system has the potential to further improve the efficiency of gene-editing applications and molecular biology studies in maize.
-
Translatable gene therapy for lung cancer using Crispr CAS9-an exploratory review.
Gene therapy using CRISPR Cas9 technique is rapidly gaining popularity among the scientific community primarily because of its versatility, cost-effectiveness, and high efficacy. While the laboratory-based experiments and findings making use of CRISPR as a gene editing tool are available in ample amounts, the question arises that how much of these findings are actually translatable into measures helping in combating particular disease conditions. In this review, we highlight the important studies and findings done till now in the perspective of lung cancer with an in-depth analysis of various clinical trials associated with the use of CRISPR Cas9 technology in the field of cancer research.
-
CRISPR catch-up.
-
Modulation of DNA double-strand break repair as a strategy to improve precise genome editing.
In the present day, it is possible to incorporate targeted mutations or replace a gene using genome editing techniques such as customisable CRISPR/Cas9 system. Although induction of DNA double-strand breaks (DSBs) by genome editing tools can be repaired by both non-homologous end joining (NHEJ) and homologous recombination (HR), the skewness of the former pathway in human and other mammals normally result in imprecise repair. Scientists working at the crossroads of DNA repair and genome editing have devised new strategies for using a specific pathway to their advantage. Refinement in the efficiency of precise gene editing was witnessed upon downregulation of NHEJ by knockdown or using small molecule inhibitors on one hand, and upregulation of HR proteins and addition of HR stimulators, other hand. The exploitation of cell cycle phase differences together with appropriate donor DNA length/sequence and small molecules has provided further improvement in precise genome editing. The present article reviews the mechanisms of improving the efficiency of precise genome editing in several model organisms and in clinics.
-
Prime editing using CRISPR-Cas12a and circular RNAs in human cells.
Genome editing with prime editors based on CRISPR-Cas9 is limited by the large size of the system and the requirement for a G/C-rich protospacer-adjacent motif (PAM) sequence. Here, we use the smaller Cas12a protein to develop four circular RNA-mediated prime editor (CPE) systems: nickase-dependent CPE (niCPE), nuclease-dependent CPE (nuCPE), split nickase-dependent CPE (sniCPE) and split nuclease-dependent CPE (snuCPE). CPE systems preferentially recognize T-rich genomic regions and possess a potential multiplexing capacity in comparison to corresponding Cas9-based systems. The efficiencies of the nuclease-based systems are up to 10.42%, whereas niCPE and sniCPE reach editing frequencies of up to 24.89% and 40.75% without positive selection in human cells, respectively. A derivative system, called one-sniCPE, combines all three RNA editing components under a single promoter. By arraying CRISPR RNAs for different targets in one circular RNA, we also demonstrate low-efficiency editing of up to four genes simultaneously with the nickase prime editors niCPE and sniCPE.
-
Determination of Factors Driving the Genome Editing Field in the CRISPR Era Using Bibliometrics.
Over the past two decades, the discovery of CRISPR-Cas immune systems and the repurposing of their effector nucleases as biotechnological tools have revolutionized genome editing. The corresponding work has been captured by 90,000 authors representing 7,600 affiliations in 126 countries, who have published more than 19,000 papers spanning medicine, agriculture, and biotechnology. Here, we use tech mining and an integrated bibliometric and networks framework to investigate the CRISPR literature over three time periods. The analysis identified seminal papers, leading authors, influential journals, and rising applications and topics interconnected through collaborative networks. A core set of foundational topics gave rise to diverging avenues of research and applications, reflecting a bona fide disruptive emerging technology. This analysis illustrates how bibliometrics can identify key factors, decipher rising trends, and untangle emerging applications and technologies that dynamically shape a morphing field, and provides insights into the trajectory of genome editing.
-
CRISPR-Edited Stem Cell Transplantation for HIV-Related Gene Modification In Vivo: A Systematic Review.
BACKGROUND: CRISPR is a novel genomic editing technology which can be useful for the treatment of immune diseases such as HIV. However, the application of CRISPR in stem cells for HIV-related research was not effective, and most of the research was done in vivo. This systematic review is to identify a new research idea about increase CRISPR-editing efficiencies in stem cell transplantation for HIV treatment, as well as its future perspective. METHOD: Four databases were searched for articles published during 1952 to 2020. PRISMA method was used to select appropriate research papers. CAMARADES was used to identify the paper quality. The outcome was engraftment efficiency, gene disruption percentage, differentiation ability, HIV-resistant efficiency. RESULT: Screening method showed 196 papers mentioned the topic. However, only 5 studies were reliable with the research objective. We found that (1) Two research ideas which was double gene knockout and knockout-knockin method to provide HIV-resistant cells, engraftment support and avoid cardiac disease as an HIV disease side effect. (2) Ribonucleoprotein (RNP) delivery was the best way to deliver the CRISPR/Cas9 and Adeno-Associated Virus (AAV) would be effective for knockin purpose. (3) CRISPR/SaCas9 could replace CRISPR/Cas9 role in editing HIV-related gene. CONCLUSION: Potential genes to increase HIV resistance and stem cell engraftment should be explored more in the future. Double knockout and knock-in procedures should be applied to set up a better engraftment for improving HIV treatment or resistance of patients. CRISPR/SaCas9 and RNP delivery should be explored more in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020203312.
-
Wake-up Sleepy Gene: Reactivating Fetal Globin for β-Hemoglobinopathies.
Disorders in hemoglobin (hemoglobinopathies) were the first monogenic diseases to be characterized and remain among the most common and best understood genetic conditions. Moreover, the study of the β-globin locus provides a textbook example of developmental gene regulation. The fetal γ-globin genes (HBG1/HBG2) are ordinarily silenced around birth, whereupon their expression is replaced by the adult β-globin genes (HBB primarily and HBD). Over 50 years ago it was recognized that mutations that cause lifelong persistence of fetal γ-globin expression ameliorate the debilitating effects of mutations in β-globin. Since then, research has focused on therapeutically reactivating the fetal γ-globin genes. Here, we summarize recent discoveries, focusing on the influence of genome editing technologies, including CRISPR-Cas9, and emerging gene therapy approaches.
PubMed отдаёт не больше 10 000 первых результатов — уточните запрос, чтобы увидеть остальные.