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PubMed2026

RNA splicing and cardiovascular disease: a guide for cardiologists.

Alternative splicing (AS) is a fundamental RNA processing mechanism, which generates different RNA transcripts and consequently different protein isoforms from a single gene. This increases the diversity of proteins within an organism and can fine-tune biological processes. This review examines how cardiac-enriched RNA-binding proteins establish heart-specific splicing programs governing aspects of cardiac development, function, and disease. Developmentally, coordinated sarcomeric isoform switches underpin the foetal-to-adult transition and further isoform rewiring in ion channel and kinase genes determine electrophysiology and excitation-contraction coupling. AS contributes to the pathogenesis of several cardiomyopathies and emerging datasets suggest that pathological hypertrophy engages distinct splicing signatures compared with physiological hypertrophy. This review summarizes diagnostic and prognostic opportunities arising from bulk, long-read, and single-cell/nucleus transcriptomics, which resolve cell type-specific isoforms and disease-associated switches. Circulating RNA biomarkers (including splice ratios and circularRNAs) may signify myocardial remodelling and arrhythmic risk. Integrative approaches that link AS with proteomics and genomics improve variant interpretation, reveal previously unannotated protein isoforms, and enable tracking of disease progression and therapy response. Finally, an outline of therapeutic strategies to modulate AS in cardiovascular disease (CVD), including antisense oligonucleotides, small molecules, and genome-editing modalities (CRISPR, base, and prime editing), is provided. The major challenges that remain before splice-targeting therapeutics can be targeted to treat cardiovascular disease are highlighted. Lessons from neuromuscular indications establish clinical feasibility of splicing correction and motivate translation to cardiology. Together, mechanistic insight, biomarker development, and therapeutic innovation position RNA splicing as a tractable axis for precision cardiovascular medicine.

Humans↗
PubMed2026

A genetic manipulation tool based on the GP35 recombinase for targeted gene editing in mycoplasmas of ruminants.

Pathogenic ruminant mycoplasmas are major etiological agents in cattle and small ruminants and are responsible for substantial economic losses in the livestock industry. Progress in pathogenesis research and vaccine development has been hampered by a lack of effective genetic tools. The applicability of common genome editing platforms, such as CRISPR, is inherently restricted in these organisms owing to their minimal genomes, the absence of a cell wall, and low homologous recombination efficiency. Although transposon-mediated random mutagenesis and single-base editing are currently used in the editing of bovine mycoplasma, the stochastic nature of transposons, the risk of single-base random deamination, and limitations in editing window selection hinder the genetic manipulation of bovine mycoplasma. Here, we introduce a plasmid-based methodology that employs the GP35 recombinase from bacteriophage SPP1 to mediate long single-stranded DNA (ssDNA) recombineering, thereby enabling precise gene insertions and deletions in Mycoplasma bovis, with a positive-editing rate of 77.78% - 100%. This targeted system eliminates the risk of random deamination. Leveraging this tool, we generated a panel of M. bovis mutants affecting metabolic and virulence genes and obtained key insights into Mb0564, identified as a novel adhesin. The 192 to 287 aa region of GP35 is critical for interaction with SSB. Structural conservation analysis further suggested that this GP35-ssDNA editing system possesses a high potential for translation to other ruminant pathogens. Collectively, our approach expands the existing genetic toolkit for M. bovis, advances synthetic biology and M. bovis pathobiology, facilitates vaccine development, and strengthens the control of high-impact livestock diseases in line with the One Health framework.

Animals↗
PubMed2025

Prime editing in bacteria with BacPE.

Programmable genome editing technologies have revolutionized the ability of researchers to alter the genomes of microorganisms in a straightforward and efficient manner, significantly advancing the field of microbiology. To date, several CRISPR-Cas-based genome-editing systems have been developed for use in E. coli, including CRISPR/Cas9, base editing, and prime editing technologies. In this chapter, we describe the design and experimental application of BacPE, a variant of prime editing technology optimized for E. coli. BacPE facilitates the introduction of point mutations, insertions, and deletions without the need for double-strand DNA breaks. We demonstrate that BacPE is a powerful tool for genome editing in E. coli and highlight its potential applicability to other bacterial species.

Gene Editing↗
PubMed2026

Advances in Precision Editing Therapies for Alpha-1 Antitrypsin Deficiency.

Genome and RNA editing modalities have revolutionized precision gene therapy, offering a safer alternative to traditional gene replacement approaches. Alpha-1 antitrypsin deficiency (AATD) is a compelling model for precision medicine because the disease mechanism is well defined-mutations in a single gene are responsible for both liver and lung pathology. In this review, we summarize the current preclinical and clinical efforts for AATD, with an emphasis on genome and RNA editing strategies.

Humans↗
PubMed2006

[The innate antiretroviral defense of human cells, based on the DNA editing].

The editing process may play an essential role in the antiviral cell defense. The human cytidine deaminase APOBEC3G, that catalyses the deoxycytidine to deoxyuridine deamination reaction in the reverse transcript of the HIV-1 genome, leads to instability of the viral DNA, if only HIV-1 virion is defective and lacks the Vif protein. This mechanism has an affect on G-A hipermutation appearing in the provirus DNA and defective HIV-1 viral RNA, yielded in infected cell. Such hipermutation has previously been discovered in the viral HIV-1 genome, produced in peripheral blood mononuclears that were long-term cultured after collection from infected patient. Probably, the deamination reaction that is inhibited in the wild type HIV-1 by the Vif protein, occurs rarely during infection and thus increases viral diversity and drug's resistance. In this review, we present the results of latest studies concerning the mechanism of viral DNA deamination, specifity of this process and APOBEC3G - HIV-1 Vif interactions, that may be useful in designing the new anti-HIV therapies.

APOBEC-3G Deaminase↗
PubMed2025

Efficient genome editing in Pseudomonas syringae pv. actinidiae using the CRISPR/FnCas12a system.

CRISPR-based gene editing has rarely been studied in plant pathogens. In this report, the CRISPR/FnCas12a system was successfully established for gene editing in Pseudomonas syringae pv. actinidiae (Psa), which causes bacterial canker (BC) of kiwifruit. The system was constructed in a Psa-suitable vector pBBR1-MCS2 to edit hopH1 or/and hopZ5, which encode effectors only present in Psa biovar 3 (Psa3) responsible for BC pandemic in kiwifruit worldwide. Two different CRISPR RNAs (crRNA) were designed to edit either hopH1 or/and hopZ5, and two different sets of PCR primers were used to screen deletions of the target genes and the presence of the vector in Psa. The deletion in Psa was impacted by the position of the DNAs targeted by the crRNAs. The vector-eliminated mutant could receive the editing system iteratively. Interestingly, the double mutant ΔhopZ5ΔhopH1 showed significantly stronger virulence than the wild-type Psa on Actinidia eriantha cv. White (resistant to BC), but weak virulence on A. chinensis cv. Hongyang (highly susceptible to BC), respectively, suggesting that hopH1 or/and hopZ5 potentially matches an unknown resistance gene in White. In summary, we have established the CRISPR/FnCas12a genome-editing system to probe gene function in the pathogen and to explore effector-target interactions in kiwifruit-Psa-pathosyetem.

Bacterial canker↗
PubMed1998

Evolutionary analysis of RNA editing enzymes.

This article focuses on the evolution of apolipoprotein B (apoB) mRNA editing. We review the tools commonly used in homology search and phylogenetic analysis and demonstrate their use in the analysis of RNA-editing enzymes. The ultimate goal is to apply these tools to answer two questions: How did apoB mRNA editing come about? How might it be related to other base substitution editing in the course of evolution.

APOBEC-1 Deaminase↗
PubMed2004

Gene editing of a human gene in yeast artificial chromosomes using modified single-stranded DNA and dual targeting.

A single-nucleotide polymorphism (SNP) in a human gene can alter the behavior of the corresponding protein, and thereby affect an individual's response to drug therapy. Here, we describe a novel dual-targeting approach for introducing an SNP of choice into virtually any gene, through the use of modified single-stranded oligonucleotides (MSSOs). We use this strategy to create SNPs in a human gene contained in a yeast artificial chromosome (YAC). In the dual-targeting protocol, two different MSSOs are designed to edit two different bases in the same cell. A change in one of these genes is selective while the other is non-selective. We show that the population identified by selective pressure is enriched for cells that bear an edited base at the nonselective site. YACs with human genomic inserts containing particular SNPs or haplotypes can be used for pharmacogenomic applications, in cell lines and in transgenic animals.

Base Sequence↗
PubMed2025

Development of a highly efficient protoplast regeneration and transfection protocol for enhancing CRISPR genome editing of Brassica carinata.

Brassica carinata is an important oil crop with significant potential for food and industrial production. The application of the CRISPR/Cas9 genome editing tool in B. carinata could accelerate its breeding cycle. However, no efficient DNA-free gene editing method currently exists for this species. Protoplast-based CRISPR editing presents a promising solution, though it is often challenging for many crop species. In this study, we investigated several critical factors influencing in vitro shoot regeneration, including genotype, sugar type, selection and combination of plant growth regulators (PGRs), and culture duration on different media throughout various stages of protoplast development. As a result, we developed a highly efficient, five-stage protoplast regeneration protocol for B. carinata based on specific stages of protoplast development. Key findings of this study include the requirement for high concentrations of NAA and 2,4-D in the initial medium (MI) for cell wall formation, while a lower auxin concentration relative to cytokinin was necessary for active cell division (MII). For callus growth and shoot induction, a high cytokinin-to-auxin ratio was essential (MIII), and an even higher cytokinin-to-auxin ratio was optimal for shoot regeneration (MIV). For shoot elongation, low levels of BAP and GA3 were sufficient (MV). Our results also demonstrated that the duration of culture on different media and maintaining appropriate osmotic pressure at the early stages were crucial for successful protoplast regeneration. With this optimized protocol, we achieved an average regeneration frequency of up to 64% and a transfection efficiency of 40% using the GFP marker gene. This efficient protoplast regeneration protocol is now being employed for genome editing in our lab and is expected to significantly enhance the application of the CRISPR system in both basic research and the genetic improvement of B. carinata over the long term.

Brassica carinata↗
PubMed2002

RNA sequence and base pairing effects on insertion editing in Trypanosoma brucei.

RNA editing inserts and deletes uridylates (U's) in kinetoplastid mitochondrial pre-mRNAs by a series of enzymatic steps. Small guide RNAs (gRNAs) specify the edited sequence. Editing, though sometimes extensive, is precise. The effects of mutating pre-mRNA and gRNA sequences in, around, and upstream of the editing site on the specificity and efficiency of in vitro insertion editing were examined. U's could be added opposite guiding pyrimidines, but guiding purines, particularly A's, were required for efficient ligation. A base pair between mRNA and gRNA immediately upstream of the editing site was not required for insertion editing, although it greatly enhanced its efficiency and accuracy. In addition, a gRNA/mRNA duplex upstream of the editing site enhanced insertion editing when it was close to the editing site, but prevented cleavage, and hence editing, when immediately adjacent to the editing site. Thus, several aspects of mRNA-gRNA interaction, as well as gRNA base pairing with added U's, optimize editing efficiency, although they are not required for insertion editing.

Animals↗
PubMed2026

Phytoplasma-plant interactions: effector-mediated host reprogramming, hormonal crosstalk, metabolic alterations and plant-mediated vector manipulation.

Phytoplasmas are wall-less, phloem-restricted bacterial pathogens that infect over 1,000 plant species, causing substantial losses in agriculture, horticulture, and forestry worldwide. Despite their reduced genomes and limited metabolic autonomy, these obligate parasites colonize diverse hosts through secreted effector proteins that extensively reprogram plant development, metabolism, immune signalling, and vector interactions. Advances in genomics, transcriptomics, proteomics, metabolomics, and functional studies have substantially clarified the molecular basis of phytoplasma pathogenicity and symptom development. This review synthesizes current understanding of phytoplasma-plant interactions, covering phytoplasma biology, genome evolution, and the infection cycle across plant and insect vector hosts. We examine the molecular functions of key effectors, SAP11, SAP54/PHYL1, SAP05, TENGU, SWP1, and recently identified virulence factors, focusing on how they target host transcription factors, phytohormone networks, protein degradation pathways, and immune responses to promote colonization and disease progression. We further discuss how phytoplasma infection disrupts phytohormone signalling, primary and secondary metabolism, and developmental programs to produce characteristic disease symptoms, with particular attention to pathogen-induced changes in host volatiles and nutritional quality that alter vector behaviour and enhance transmission. Finally, we summarize insights from multi-omics studies and emerging management strategies, including CRISPR-based genome editing, RNAi, rapid molecular diagnostics, resistant cultivars, microbiome-based approaches, and sustainable vector control, and highlight key knowledge gaps and priorities for developing effective, environmentally sustainable phytoplasma disease management.

Phytoplasma↗
PubMed2026

Research note: Efficient preservation of genome-edited chicken germplasm via N-methylacetamide-based semen cryopreservation.

The rapid development of genome-edited chicken lines for agricultural and biomedical use requires effective methods for long-term preservation. In birds, cryopreservation of oocytes and embryos is challenging due to the structure of the egg. This makes semen cryopreservation one of the most practical alternatives, however, this method has not been validated in genome-edited chickens. This study evaluated the feasibility of cryopreserving semen from genome-edited chickens using an N-methylacetamide (N-MA)-based protocol. Two genome-edited chicken lines were used in this study which are a DAZL-GFP germ cell reporter line and a RAG1 knockout line. Semen was stored for either one week or one month prior to assessing fertility and hatchability. The results demonstrated that cryopreserved semen from both genome-edited chicken lines maintained their fertilizing capacity, with no significant differences in fertility or hatchability compared to cryopreserved wild-type groups at either storage duration. Hatchability remained above 80% across all groups, indicating that semen cryopreservation did not significantly affect embryo development after successful fertilization. Furthermore, SYBR-14/PI staining revealed no significant differences in sperm viability between genome-edited and control groups, although both showed a significant decrease in viability compared to fresh semen. These findings demonstrate that N-MA-based semen cryopreservation provides a reliable and practical method for the preservation of genome-edited chicken lines.

Chicken↗
PubMed2006

RNA editing in plant organelles: machinery, physiological function and evolution.

In plants, RNA editing is a process for converting a specific nucleotide of RNA from C to U and less frequently from U to C in mitochondria and plastids. To specify the site of editing, the cis-element adjacent to the editing site functions as a binding site for the trans-acting factor. Genetic approaches using Arabidopsis thaliana have clarified that a member of the protein family with pentatricopeptide repeat (PPR) motifs is essential for RNA editing to generate a translational initiation codon of the chloroplast ndhD gene. The PPR motif is a highly degenerate unit of 35 amino acids and appears as tandem repeats in proteins that are involved in RNA maturation steps in mitochondria and plastids. The Arabidopsis genome encodes approximately 450 members of the PPR family, some of which possibly function as trans-acting factors binding the cis-elements of the RNA editing sites to facilitate access of an unidentified RNA editing enzyme. Based on this breakthrough in the research on plant RNA editing, I would like to discuss the possible steps of co-evolution of RNA editing events and PPR proteins.

Chloroplasts↗
PubMed1991

A trace display and editing program for data from fluorescence based sequencing machines.

'Ted' (Trace editor) is a graphical editor for sequence and trace data from automated fluorescence sequencing machines. It provides facilities for viewing sequence and trace data (in top or bottom strand orientation), for editing the base sequence, for automated or manual trimming of the head (vector) and tail (uncertain data) from the sequence, for vertical and horizontal trace scaling, for keeping a history of sequence editing, and for output of the edited sequence. Ted has been used extensively in the C.elegans genome sequencing project, both as a stand-alone program and integrated into the Staden sequence assembly package, and has greatly aided in the efficiency and accuracy of sequence editing. It runs in the X windows environment on Sun workstations and is available from the authors. Ted currently supports sequence and trace data from the ABI 373A and Pharmacia A.L.F. sequencers.

Animals↗
PubMed2003

[Exploration on the mother edition of Wang Bing's annotated Su wen (Plain questions)].

According to Wang Bing's preface, when arranging Su wen (Plain Questions), he applied different editions of the book. But, he didn't indicate which edition was applied as the mother edition. By analyzing materials from Wang's preface, newly produced Plain Questions, etc. though the mother edition he used was based on the edition of the Liang dynasty, it was not the edition of Quan Yuanqi, but a clandestine edition of Master Zhang. Some of the chapters and texts of now extant Plain Questions editions should be the old original of the mother edition. The mother edition, Quan Yuanqi's edition, Zhen jiu jia yi jing (A-B Classic of Acupuncture and Moxibustion) and Tai su (Extremely Plain) are derived from different editions.

Books↗