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At least 127 records · Page 7Linked to original sources
PubMed1991

Ambulatory blood pressure monitoring in clinical trials.

Monitoring ambulatory blood pressure, instead of taking pressure readings in hospital, avoids the so-called white-coat effect and allows more readings to be obtained over a longer period of time. It improves the accuracy of the blood pressure estimate and increases the statistical power of therapeutic trials for hypertension. Subjects with white-coat or office hypertension can be detected by ambulatory blood pressure monitoring and excluded from clinical trials. In 23 studies, including a total of 3304 normotensive subjects, the 24-h ambulatory blood pressure averaged 118/72 mmHg; the daytime and night-time pressures were 123/76 mmHg and 106/64 mmHg, respectively. If the mean plus two standard deviation (s.d.) interval is considered the upper limit of normal, the meta-analysis suggested that hypertension may be suspected if the 24-h pressure exceeds 129/87 mmHg, or if the daytime or night-time pressures are higher than 146/91 mmHg or 127/79 mmHg, respectively. On balance, most studies suggest that placebo effects on blood pressure are not observed when blood pressure is measured with ambulatory recorders. If confirmed, this observation indicates that it is possible to simplify the design of trials in the field of hypertension. Ambulatory blood pressure readings should be obtained with properly validated monitors. If the recordings are of sufficient quality, editing does not increase the precision of the subsequent statistical analyses. The statistical analyses should account for diurnal rhythms, and subject and treatment effects.

Antihypertensive Agents↗
PubMed2026

Engineered Transformer Base Editor with Enhanced Editing Efficiency.

Canonical cytosine base editors (CBEs) achieve precise C-to-T conversions without inducing DNA double-strand breaks (DSBs), yet their clinical potential remains hampered by substantial off-target (OT) mutations. The recently developed transformer base editor (tBE) significantly reduces both genomic and transcriptomic OT mutations by using a cleavable deoxycytidine deaminase inhibitor (dCDI) domain. However, the modest base editing efficiency limits its broader applications. Here, through rational deaminase engineering and fusion of a uracil DNA glycosylase inhibitor (UGI) domain, we developed the engineered tBE (etBE). The etBE exhibited substantially enhanced editing efficiencies compared with the parental tBE (up to 35.11-fold improvement), while maintaining high editing fidelity and background levels of OT mutations. As a therapeutic proof-of-concept, dual adeno-associated virus (AAV)-mediated delivery of etBE targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-established therapeutic target for cardiovascular diseases, was evaluated in a humanized mouse model. The treatment achieved efficient in vivo base editing (up to 35.13%), resulting in substantial reductions in plasma PCSK9 protein (24%) and low-density lipoprotein cholesterol (LDL-C) levels (33%), while inducing only minimal OT mutations. Collectively, etBE represents a highly efficient and specific base editing platform with enormous potential for both basic research and clinical applications.

CRISPR‐Cas9↗
PubMed2026

Holistic approaches for improvement of maize resistance against lodging stress: current status and future perspective.

Lodging is a major constraint in maize production, causing significant yield losses, reduced grain quality, and harvesting inefficiencies, thereby posing a serious challenge to global food security and climate-resilient agriculture. This review synthesizes current knowledge on the genetic, physiological, and agronomic determinants of maize lodging resistance and evaluates holistic strategies for improving tolerance to lodging stress. Recent advances in quantitative trait locus (QTL) mapping, genome-wide association studies (GWAS), functional gene characterization, genome editing, high-throughput phenotyping, and precision agronomy have provided powerful tools to enhance stalk biomechanics, root anchorage, and adaptive plant architecture. Integrating genomic discovery with advanced phenomics and optimized agronomic management offers a scalable framework for accelerating the development of high-yielding, lodging-resilient maize cultivars. However, critical gaps remain in understanding the genetic coordination between stalk strength and root system architecture, integrating multi-omics approaches to unravel regulatory networks, validating genome-editing interventions across diverse agro-ecologies, and developing environment-responsive predictive breeding models and cost-effective phenotyping tools, particularly for stress-prone regions. Addressing these challenges through coordinated multi-environment trials and integrative molecular-agronomic strategies will facilitate the translation of genomic discoveries into climate-resilient, high-performing maize cultivars. By consolidating molecular insights with applied breeding and management practices, this review provides a comprehensive framework that guides researchers in designing genome-informed and field-validated approaches to improve maize resistance to lodging stress and support sustainable crop production systems.

Zea mays↗
PubMed1996

Hyperediting of multiple cytidines of apolipoprotein B mRNA by APOBEC-1 requires auxiliary protein(s) but not a mooring sequence motif.

An RNA-binding cytidine deaminase (APOBEC-1) and unidentified auxiliary protein(s) are required for apolipoprotein (apo) B mRNA editing. A sequence motif on apoB mRNA ("mooring sequence," nucleotides 6671-6681) is obligatory for the editing of cytidine 6666 (C6666), the only cytidine on apoB mRNA converted to uridine in normal animals. Transgenic animals with hepatic overexpression of APOBEC-1 develop liver tumors, and other non-apoB mRNAs are edited, suggesting a loss of the normally precise specificity. In this study, we examined apoB mRNA from these transgenic animals to determine if cytidines aside from C6666 are edited. Multiple cytidines downstream from C6666 in apoB mRNA were edited extensively by the overexpressed APOBEC-1. This pathophysiological "hyperediting" could be mimicked in vitro by incubating a synthetic apoB RNA substrate with the transgenic mouse liver extracts. Multiple cytidines in the synthetic apoB RNA were edited by recombinant APOBEC-1 but only with supplementation of the auxiliary protein(s). Mutations in the mooring sequence markedly decreased the normal editing of C6666 but, surprisingly, increased the hyperediting of downstream cytidines. Furthermore, cytidines in an apoB RNA substrate lacking the mooring sequence were also edited in vitro. These results indicate that the hyperediting of apoB mRNA by overexpressed APOBEC-1 depends upon auxiliary protein(s) but is independent of the mooring sequence motif. These results suggest that hyperediting may represent the first step in a two-step recognition model for normal apoB mRNA editing.

APOBEC-1 Deaminase↗
PubMed2025

dCas-Based Tools to Visualize Chromatin or Modify Epigenetic Marks at Specific Plant Genomic Loci.

Development of locus-specific approaches targeting precise regions on chromatin, for locus/transcription visualization or transcription/epigenetic marks editing, is a critical challenge in functional genetics and epigenetics. Systems engineered from the clustered regularly interspaced short palindromic repeats (CRISPR) and its associated endonuclease (Cas) operate through DNA sequence-specific recognition by so-called guide RNAs, which provides high flexibility and modularity for precise chromatin visualization or edition. Here, we provide an overview of the CRISPR/Cas-derived tools developed for visualization of chromatin loci in live imaging or for effective modification of gene expression. These tools make use of effector modules that combine activators, repressors, and epigenetic modifiers with a deactivated Cas protein (dCas). We present how their use in plants brought advances in visualizing or manipulating the expression of loci involved in agronomically interesting traits such as flowering time and response to drought or heat. We also discuss the limitations and future improvements of the dCas-related technologies, such as more compact and combinatorial systems, spatiotemporal targeting for fine-tuning of gene expression, and live visualization of chromatin dynamics.

Chromatin↗
PubMed2026

The emerging impact of CRISPR and gene editing on global crop improvement.

The advent of CRISPR-based genome editing has revolutionized crop improvement, offering unprecedented precision and efficiency in modifying key agronomic traits. This review comprehensively examines the mechanisms, applications, and future potential of CRISPR technology in enhancing global crop production. CRISPR-Cas systems, originally identified as adaptive immune mechanisms in bacteria and archaea, have been repurposed for targeted genome editing in plants. The CRISPR-Cas9 system, in particular, has emerged as a powerful tool for introducing site-specific double-strand breaks, enabling precise genetic modifications. The three-stage process of adaptation, expression, and interference underlies the CRISPR mechanism, with guide RNAs directing Cas endonucleases to specific genomic loci. Advances in CRISPR technology have expanded its applications beyond gene knockouts, encompassing base editing, prime editing, and epigenome editing. These innovations have facilitated the development of crops with enhanced yield, stress tolerance, disease resistance, nutritional content, and post-harvest quality. However, challenges related to off-target effects, regulatory hurdles, ethical concerns, and public acceptance must be addressed to fully harness the potential of CRISPR in agriculture. Integration of CRISPR with other cutting-edge technologies, such as synthetic biology, artificial intelligence, and high-throughput phenotyping, holds immense promise for accelerating crop improvement efforts. As research continues to refine CRISPR tools and expand their applicability across diverse plant species, this transformative technology is poised to play a pivotal role in shaping a sustainable, resilient, and productive global food system for future generations.

Gene Editing↗
PubMed2026

Inheritance of the epigenetic signature and reduced intermuscular bone phenotype acquired via DNA methylation editing of the runx2 b promoter in zebrafish.

The presence of intermuscular bones (IBs) can directly affect the economic value of aquaculture fish. Although genome editing can create IB-free fish by knocking out key IB-related genes, such as runx2b, the associated DNA sequence alterations raise food safety and health concerns, limiting its breeding applications. In this study, we used CRISPR/dCas9-mediated epigenome-editing technology targeting the runx2 b promoter in zebrafish to alter DNA methylation patterns without changing the DNA sequence. Our results showed that higher runx2 b promoter methylation patterns significantly inhibited eGFP mRNA expression levels in the recombinant plasmid. Using the CRISPR/dCas9-Dnmt7 system to enhance methylation of the zebrafish runx2b promoter, we observed a significant decrease in runx2 b mRNA expression levels in the F0 generation. The IBs in the 11 th-16 th muscle segments of the adult F0 fish were significantly shorter compared with the controls. Inbreeding of fish was used to produce F1 and F2 offspring that retained these high promoter methylation levels, along with persistent runx2b expression suppression and IB development inhibition. Transcriptome sequencing analysis suggested that increasing runx2 b promoter methylation levels may synergistically induce additional epigenetic modifications, potentially affecting the PPAR signaling pathway and FoxO transcription factor regulation, which appears to inhibit osteoblast proliferation and differentiation. Overall, this study demonstrates an innovative application of epigenetic editing technology for aquaculture breeding. By precisely regulating the expression patterns of key genes for economically important traits while preserving genomic DNA integrity, this approach provides a theoretical foundation and technical support for improving fish economic traits.

Animals↗
PubMed2000

[Basic principles of data acquisition and data processing for construction of high quality virtual models].

Creating models for virtual reality subdivides into several steps. The aim of the data acquisition is the extraction of nearly isotropic (same solution in all three axes) data sets with low noise content. An approximate isotropy can be achieved by suitable choice of scan parameters. For raw data reconstruction, the application of high-resolution reconstruction algorithms is prohibited due to increased noise. A missing isotropy can computationally be approximated by interpolation. Further noise suppression is achieved by applying filters. Additionally, the contrast of the object for segmentation can be increased by image processing operators. The correct choice of the segmentation method and the editing tools is essential for a precise segmentation with minimal user interaction. Prior to visualization, smoothing the shape of the segmented model (shape-based or morphological interpolation, polygon reduction of wire frame model) further improves the visual appearance of the 3D model.

Algorithms↗
PubMed1991

Cycles of progressive realignment of gRNA with mRNA in RNA editing.

We characterized numerous partially edited NADH dehydrogenase 7 and ATPase 6 cDNAs. Most of these have a stretch of incompletely edited sequence at the junction of mature and unedited sequences. The characteristics of the junctions suggest editing of sites multiple times and that editing within each junction does not proceed precisely 3' to 5'. Analyses of gRNAs and corresponding junction sequences predict a series of progressively more stable, but incompletely base-paired, interactions in the junction region. The predicted interactions suggest that the gRNA is progressively realigned with the mRNA being edited. We suggest that gRNA interactions with the mRNA result in regions of lower thermodynamic stability that are selected for editing, thus driving toward the most stable structure, the complete gRNA/mRNA duplex.

Adenosine Triphosphatases↗
PubMed2002

Protein splicing triggered by a small molecule.

The use of small molecules that turn specific proteins on or off provides a level of temporal control that is difficult to achieve using standard genetic approaches. Consequently, the development of small-molecule switches of protein function is a very active area of chemical biology, sometimes referred to as chemical genetics. Most studies in this area rely on the identification of small molecules that bind directly to the active site of a target protein, thereby acting as agonists or antagonists of function. Strategies have also been described in which the small molecule triggers a change in the secondary, tertiary, or ternary structure of the protein, in so doing changing the functional state of the molecule. Another approach to this problem would be to alter the primary structure of a target protein in response to a small-molecule trigger; a dramatic change in primary sequence would be directly coupled to function. In principle, this can be achieved by harnessing protein splicing, a posttranslational editing process that results in the precise removal of an internal domain (termed an intein) from two flanking sequences termed the N- and C-exteins. In this communication we introduce a technique that allows protein splicing to occur only in the presence of the small molecule, rapamycin. This approach is expected to be independent of the nature of the two exteins and so should provide a general vehicle for controlling protein function using small molecules.

Blotting, Western↗
PubMed2025

Treatment of a severe vascular disease using a bespoke CRISPR-Cas9 base editor in mice.

Pathogenic missense mutations in the alpha actin isotype 2 (ACTA2) gene cause multisystemic smooth muscle dysfunction syndrome (MSMDS), a genetic vasculopathy that is associated with stroke, aortic dissection and death in childhood. Here we perform mutation-specific protein engineering to develop a bespoke CRISPR-Cas9 enzyme with enhanced on-target activity against the most common MSMDS-causative mutation ACTA2 R179H. To directly correct the R179H mutation, we screened dozens of configurations of base editors to develop a highly precise corrective A-to-G edit with minimal deleterious bystander editing that is otherwise prevalent when using wild-type SpCas9 base editors. We create a murine model of MSMDS that shows phenotypes consistent with human patients, including vasculopathy and premature death, to explore the in vivo therapeutic potential of this strategy. Delivery of the customized base editor via an engineered smooth muscle-tropic adeno-associated virus (AAV-PR) vector substantially prolongs survival and rescues systemic phenotypes across the lifespan of MSMDS mice, including in the vasculature, aorta and brain. Our results highlight how bespoke mutant-specific CRISPR-Cas9 enzymes can improve mutation correction with base editors.

Animals↗
PubMed2026

Impact of wheat GRF4-GIF1 morphogenic regulators on transformation and genome editing efficiency in elite barley cultivars.

INTRODUCTION: Efficient genetic transformation is essential for the delivery of the CRISPR/Cas9 genome editing system and thus represents an important technology for breeding-oriented research in barley (Hordeum vulgare L.). However, transformation and plant regeneration from tissue culture remain challenging in non-model barley genotypes. Previous studies demonstrated that expression of a chimeric fusion between two interacting transcription factors, GROWTH-REGULATING FACTOR 4 (GRF4) and GRF-INTERACTING FACTOR 1 (GIF1), enhances regeneration capacity in wheat and other species. METHODS: In this study, we evaluated the effect of the wheat-derived GRF4-GIF1 morphogenic regulators on biolistic transformation and genome editing efficiency in three commercial barley cultivars: Tselinniy 5, Aley, and G-23035. RESULTS: The JD633 construct carrying GRF4-GIF1 enabled recovery of stable transformants in all three genotypes, with efficiencies ranging from 2.5% to 5%, whereas the control construct lacking morphogenic regulators resulted in no transgenic events in any of the tested varieties. Among transformed T0 plantlets, genome editing efficiency reached 64.3%, with predominantly biallelic mutations that were stably inherited in the T1 generation. Molecular screening revealed the presence of plasmid-free edited plants in the T0 generation, likely arising from transient Cas9 expression, and provided evidence of tissue chimerism. DISCUSSION: These results demonstrate that the GRF-GIF system facilitates genome editing, providing a practical framework for accelerating precision breeding in barley.

CRISPR/Cas9↗
PubMed1996

Paramyxovirus RNA editing and the requirement for hexamer genome length.

Paramyxoviruses cotranscriptionally edit their P gene mRNA by the programmed insertion of G residues into a short G run contained within a larger purine run, via pseudo-templated transcription. The templates for paramyxovirus transcription are genome nucleocapsids in which each nucleoprotein subunit is associated with 6 nt, and only genomes whose lengths are multiples of 6 are found naturally or are replicated efficiently in transfected cell systems. We have examined the effect of varying total genome length on the frequency and number of insertions into the mRNA editing site in a transfected cell system, using constructs that generate mini-genome analogues. We found that, as long as the purine run sequence and the region immediately upstream were unaltered, editing occurred during mRNA synthesis independent of the precise length of the minigenome. However, when mini-genome constructs whose lengths were not multiples of 6 were used, insertions (or deletions) occurred during antigenome synthesis within the purine run, which strikingly restored the hexamer length. Genome length correction due to changes in the antigenome purine run length occurred only when the mini-genome was not a multiple of 6, and these changes were only poorly affected by mutations in the mRNA editing site and the region immediately upstream. Our results suggest that the mRNA editing site is a natural hotspot for viral polymerase slippage during genome replication, and that this site serves the dual and complementary function of maintaining hexamer genome length. The unusual requirement of paramyxoviruses for genomes of precise hexamer length may have evolved to maintain genome stability against insertions in the mRNA editing site during replication.

Base Composition↗
PubMed2026

CRISPR/Cas in gynecologic cancers: A review of experimental and therapeutic applications.

Gynecological malignancies-including cervical, ovarian, and endometrial cancers-remain a major global health challenge, contributing significantly to cancer-related morbidity and mortality among women. Despite advances in conventional treatments such as surgery, chemotherapy, radiotherapy, and immunotherapy, issues such as drug resistance, tumor recurrence, and limited efficacy in advanced-stage disease necessitate novel therapeutic strategies. The emergence of CRISPR/Cas-based genome editing has revolutionized cancer research by enabling precise, efficient, and programmable modifications of specific genomic loci. In gynecologic oncology, CRISPR/Cas systems have been employed to dissect oncogenic mechanisms, identify therapeutic targets, and develop innovative treatment modalities. In cervical cancer, CRISPR-mediated targeting of HPV E6 and E7 oncogenes has shown potential in restoring tumor suppressor pathways and enhancing chemosensitivity. In ovarian cancer, gene editing has been used to modulate chemoresistance, tumor angiogenesis, and metastasis through the knockout of key regulators such as DNMT1, EGFL6, and BRCA1/2. Similarly, in endometrial cancer, CRISPR tools have elucidated mechanisms of hormonal resistance and facilitated the development of in vivo models via somatic gene editing. This review highlights recent advances in the application of CRISPR/Cas technology to gynecologic malignancies, discussing its potential as both a therapeutic and research platform while acknowledging current limitations and translational hurdles.

Humans↗
PubMed2002

Identification and regulation of protein components of the apolipoprotein B mRNA editing enzyme. A complex event.

Apolipoprotein B (apoB) gene expression is regulated by transcriptional, posttranscriptional, and translational mechanisms in both small intestinal enterocytes and hepatocytes of all mammals. This review focuses on the posttranscriptional regulation of apoB gene expression-specifically, an enzymatic modification to the nuclear transcript referred to as C to U RNA editing. C to U RNA editing, the process responsible for the production of apoB-48, is an exquisitely precise process that targets a single nucleotide in over 14,000. RNA editing requires regulated interactions between core enzyme components whose identity is known and regulatory factors, most of which have yet to be fully characterized. This review summarizes information relevant to those transacting factors that are essential for editing activity (core factors) as well as those interacting partners (regulatory factors) whose physiological role in RNA editing is yet to be fully defined.

APOBEC-1 Deaminase↗
PubMed2006

Alternative editing of cytochrome c oxidase III mRNA in trypanosome mitochondria generates protein diversity.

Trypanosomes use RNA editing to produce most functional mitochondrial messenger RNA. Precise insertion and deletion of hundreds of uridines is necessary to make full-length cytochrome c oxidase III (COXIII) mRNA. We show that COXIII mRNA can be alternatively edited by a mechanism using an alternative guide RNA to make a stable mRNA. This alternatively edited mRNA is translated to produce a unique protein that fractionates with mitochondrial membranes and colocalizes with mitochondrial proteins in situ. Alternative RNA editing represents a previously unknown mechanism generating protein diversity and, as such, represents an important function for RNA editing.

Amino Acid Sequence↗
PubMed2026

Emerging trends in genome editing of wild animals.

Globally, nearly one million species are currently threatened with extinction, highlighting the need for more efficient solutions to biological conservation. Genome editing, which allows for faster and more precise changes in genomes, is a promising technique for boosting populations through facilitated adaptation, management of invasive or pathogenic populations, and potentially even facilitating the revival of extinct species. These approaches belong to a new field of research termed conservation biotechnology, which places a great responsibility on researchers and decision makers to ensure sustainability. In this paper, we have mapped the emerging trends in genome editing of wild animals. Current projects primarily focus on population control and de-extinction, with fewer initiatives aimed at preserving threatened species. We then explore four critical dimensions of conservation biotechnology: the technology itself, new perspectives on conservation practices, research organization, and governance and policy. Despite its potential, key questions remain-particularly whether genome editing can increase genetic diversity without causing unintended non-target impacts. Genome editing also provokes new perspectives on conservation practices where ecosystem-wide impact assessment, case-by-case evaluations, and post-release monitoring needs to be prioritized. Furthermore, conservation biotechnology is heavily funded through private funding showing varying stakeholder interest, which can lead to untraditional and less transparent research processes. Stakeholders, including local and indigenous people, are only to a certain degree involved, which may weaken inclusion of local knowledge and monitoring efforts. Finally, concerning governance and policy, there is an urgent need to develop more adequate regulation of conservation biotechnology, as environmental release of genome-edited animals challenges definitions and guidelines in current nature protection laws and GMO regulations. Based on our analysis, we outline key points for further investigation toward a more sustainable approach to conservation biotechnology.

Animals↗
PubMed1996

In vivo dissection of cis-acting determinants for plastid RNA editing.

Substitutional RNA editing changes single C nucleotides in higher plant chloroplast transcripts into U residues. To determine the cis-acting sequence elements involved in plastid RNA editing, we constructed a series of chloroplast transformation vectors harboring selected editing sites of the tobacco ndhB transcript in a chimeric context. The constructs were inserted into the tobacco plastid genome by biolistic transformation leading to the production of stable chimeric RNAs. Analysis of RNA editing revealed unexpected differences in the size of the essential cis elements or in their distance from the editing site. Flanking sequences of identical size direct virtually complete editing for one pair of editing sites, partial editing for a second and no editing at all for a third pair of sites. Serial 5' and 3' deletions allowed us to define the cis-acting elements more precisely and to identify a sequence element essential for editing site recognition. In addition, a single nucleotide substitution immediately upstream of an editing position was introduced. This mutation was found drastically and selectively to reduce the editing efficiency of the downstream editing site, demonstrating that position -1 is important for either site recognition or catalysis. Our results indicate that the editing of adjacent sites is likely to be mechanistically coupled. In no case did the presence in the plastome of the additional editing sites have any effect on the editing efficiency of the endogenous ndhB sites, indicating that the availability of site-specific trans-acting factors is not rate limiting.

Base Sequence↗