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: 26 245
Страница 876 из 1000-
Huntington's chorea: emerging fields in therapeutics (Review).
Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and psychiatric disturbances. It is caused by CAG repeat expansions in the HTT gene, resulting in the formation of mutant huntingtin protein that aggregates and disrupts neuronal function. This review outlines the pathogenesis of HD, including genetic, molecular, and environmental factors. Additionally, current management approaches and emerging therapeutic strategies-such as RNA interference, antisense oligonucleotides (ASOs), peptide inhibitors, and CRISPR/Cas9 gene editing-are discussed. Advancements in these novel therapies highlight a shift towards disease-modifying interventions. However, continued clinical and translational research is essential to develop a definitive cure.
-
Artificial Virus Delivers CRISPR-Cas9 System for Genome Editing of Cells in Mice.
CRISPR-Cas9 has emerged as a versatile genome-editing platform. However, due to the large size of the commonly used CRISPR-Cas9 system, its effective delivery has been a challenge and limits its utility for basic research and therapeutic applications. Herein, a multifunctional nucleus-targeting "core-shell" artificial virus (RRPHC) was constructed for the delivery of CRISPR-Cas9 system. The artificial virus could efficiently load with the CRISPR-Cas9 system, accelerate the endosomal escape, and promote the penetration into the nucleus without additional nuclear-localization signal, thus enabling targeted gene disruption. Notably, the artificial virus is more efficient than SuperFect, Lipofectamine 2000, and Lipofectamine 3000. When loaded with a CRISPR-Cas9 plasmid, it induced higher targeted gene disruption efficacy than that of Lipofectamine 3000. Furthermore, the artificial virus effectively targets the ovarian cancer via dual-receptor-mediated endocytosis and had minimum side effects. When loaded with the Cas9-hMTH1 system targeting MTH1 gene, RRPHC showed effective disruption of MTH1 in vivo. This strategy could be adapted for delivering CRISPR-Cas9 plasmid or other functional nucleic acids in vivo.
-
Challenging the Boundaries Between Treatment, Prevention, and Enhancement in Human Genome Editing.
Traditional distinctions between treatment and enhancement goals for human genome editing (HGE) have animated oversight considerations, yet these categories have been complicated by the addition of prevention as a possible target for HGE applications. To assess the role these three categories might play in continued HGE governance efforts, we report on interviews with genome editing scientists and governance group members. While some accepted traditional distinctions between treatment and enhancement and rejected the latter as unacceptable, others argued that the concept of enhancement is largely irrelevant or not as morally problematic as suggested. Others described how preventive goals for HGE create gray zones where prevention and enhancement may be difficult to distinguish, which may stymie uses of HGE. We conclude by discussing the governance implications of these various understandings of treatment, prevention, and enhancement as HGE research moves beyond the treatment of serious disease to embrace longer range preventive goals.
-
Genome Editing in Brassica juncea Using CRISPR/Cas9 Technology.
Modern genome editing tools particularly CRISPR/Cas9 have revolutionized plant genome manipulation for engineering resilience against changing climatic conditions, disease infestation, as well as functional genomic studies. CRISPR-mediated genome editing allows for editing at a single as well as multiple locations in the genome simultaneously, making it an effective tool for polyploid species too. However, still, its applications are limited to the model crops only. Extending it to crop plants will help improve field crops against the changing climates more rapidly and precisely. Here we describe the protocol for editing the genome of a field crop Brassica juncea (mustard), an allotetraploid and important oilseed crop of the Indo-Pak Subcontinent region. This protocol is based on the Agrobacterium-mediated transformation for the delivery of CRISPR components into the plant genome using cotyledon as explants. We elaborate on steps for recovering genome-edited knockouts, for validation of the edits, as well as recovering the transgene-free edited plants through a commonly used segregating approach.
-
Combining Conformational Profiling of GPCRs with CRISPR/Cas9 Gene Editing Approaches.
Ligand-biased signaling could have a significant impact on drug discovery programs. As such, many approaches to screening now target a larger section of the signaling responses downstream of an individual G protein-coupled receptor (GPCR). Biosensor-based platforms have been developed to capture signaling signatures. Despite the ability to use such signaling signatures, they may still be particular to an individual cell type and thus such platforms may not be portable from cell to cell, necessitating further cell-specific biosensor development. We have developed a complementary strategy based on capturing receptor-proximal conformational profiles using intra-molecular BRET-based sensors composed of a Renilla luciferase donor engineered into the carboxy-terminus and CCPGCC motifs which bind fluorescent hairpin biarsenical dyes engineered into different positions into the receptor primary structure. Here, we discuss how these experiments can be conducted and combined with CRISPR/Cas9 genome editing to assess specific G protein-dependent and -independent events.
-
Current and future editing reagent delivery systems for plant genome editing.
Many genome editing tools have been developed and new ones are anticipated; some have been extensively applied in plant genetics, biotechnology and breeding, especially the CRISPR/Cas9 system. These technologies have opened up a new era for crop improvement due to their precise editing of user-specified sequences related to agronomic traits. In this review, we will focus on an update of recent developments in the methodologies of editing reagent delivery, and consider the pros and cons of current delivery systems. Finally, we will reflect on possible future directions.
-
Analysis of Oestrus and Hormonal Changes in the Progeny of 2 Genotypes of FecB Gene-Edited Sheep.
The FecB gene, the first gene identified for multiple births, can improve reproductive performance in sheep. We used the CRISPR/Cas9 editing system to obtain the FecB gene in Kazakh sheep and mated with unedited Kazakh sheep. After the genotypic screening of the progeny, four B+ and ++ Kazakh ewes, each 2 weeks old and healthy, and close to the same body weight, were selected to study oestrus and hormonal changes in the progeny population of FecB gene-edited Kazakh sheep. Our results showed that the FecB gene was moderately polymorphic (0.25 < PIC < 0.5) in the progeny population, was able to be stably inherited, and showed increased lambing numbers. The number of follicles and tiny follicles differed significantly (p < 0.05) between the 2 genotypes of ewes in the progeny population. Physiologically, FecB gene-edited sheep did not differ from wild-type sheep. Throughout the oestrous cycle, FSH, LH, and E2 in serum hormones of both sheep genotypes showed variability (p < 0.05) between 72-360 h, 360-528 h, and 12-72 h, respectively, compared to other periods. The concentration of FSH and PROG in follicular fluid was much higher than that of LH and E2 (p < 0.05). Overall, it is possible to make Kazakh sheep carry the FecB gene by CRISPR/Cas9 editing and stably inherit it into the progeny population. The enhancement of reproductive hormones by the FecB gene is beneficial to follicular development and ovulation and improves the reproductive efficiency of sheep.
-
New CRISPR-based strategies for Alzheimer disease.
-
[Accelerating drug discovery process with genome editing technology from Tokushima].
In a series of drug development processes from basic research to non-clinical and clinical trials, genome editing technologies have been making innovative breakthroughs. Genome editing using CRISPR/Cas9 system, which was awarded the Novel Prize in Chemistry in 2020, has greatly streamlined the production of genetically modified mice and cells, which have been used in a variety of drug discovery research and non-clinical trials. Setsuro Tech Inc. (Setsurotech) established in 2017 is a biotech startup originated in Tokushima University. In this paper, we will briefly review genome editing technology using CRISPR/Cas9 system, and then introduce our company, our fundamental technologies; GEEP method (Genome Editing by Electroporation of Cas9 Protein) developed by Takemoto et al., and VIKING method (Versatile NHEJ-based Knock-in using Genome Editing) established by Sawatsubashi et al. Also, we will introduce our contribution to the field of drug discovery research and industrial application of genome editing technology.
-
Optimized Cas9:sgRNA delivery efficiently generates biallelic MSTN knockout sheep without affecting meat quality.
BACKGROUND: CRISPR/Cas9-based genome-editing systems have been used to efficiently engineer livestock species with precise genetic alterations intended for biomedical and agricultural applications. Previously, we have successfully generated gene-edited sheep and goats via one-cell-stage embryonic microinjection of a Cas9 mRNA and single-guide RNAs (sgRNAs) mixture. However, most gene-edited animals produced using this approach were heterozygotes. Additionally, non-homozygous gene-editing outcomes may not fully generate the desired phenotype in an efficient manner. RESULTS: We report the optimization of a Cas9 mRNA-sgRNA delivery system to efficiently generate homozygous myostatin (MSTN) knockout sheep for improved growth and meat production. Firstly, an sgRNA selection software (sgRNAcas9) was used to preliminarily screen for highly efficient sgRNAs. Ten sgRNAs targeting the MSTN gene were selected and validated in vitro using sheep fibroblast cells. Four out of ten sgRNAs (two in exon 1 and two in exon 2) showed a targeting efficiency > 50%. To determine the optimal CRISPR/Cas9 microinjection concentration, four levels of Cas9 mRNA and three levels of sgRNAs in mixtures were injected into sheep embryos. Microinjection of 100 ng/μL Cas9 mRNA and 200 ng/μL sgRNAs resulted in the most improved targeting efficiency. Additionally, using both the highly efficient sgRNAs and the optimal microinjection concentration, MSTN-knockout sheep were generated with approximately 50% targeting efficiency, reaching a homozygous knockout efficiency of 25%. Growth rate and meat quality of MSTN-edited lambs were also investigated. MSTN-knockout lambs exhibited increased body weight and average daily gain. Moreover, pH, drip loss, intramuscular fat, crude protein, and shear force of gluteal muscles of MSTN-knockout lambs did not show changes compared to the wild-type lambs. CONCLUSIONS: This study highlights the importance of in vitro evaluation for the optimization of sgRNAs and microinjection dosage of gene editing reagents. This approach enabled efficient engineering of homozygous knockout sheep. Additionally, this study confirms that MSTN-knockout lambs does not negatively impact meat quality, thus supporting the adoption of gene editing as tool to improve productivity of farm animals.
PubMed отдаёт не больше 10 000 первых результатов — уточните запрос, чтобы увидеть остальные.