117 results about "Gene Deletions" patented technology

A CVB virus expression vector comprising a PIV5 W3A viral genome comprising a mutation at amino acid residue S157 or S156 of the P / V gene and a deletion of the small hydrophobic (SH) gene of the PIV5 W3A viral genome, wherein the amino acid substitution at amino acid residue S157 or S156 comprises a substitution of serine (S) with phenylalanine (F) or asparagine (N), and the SH gene has a deletion of the SH open reading frame or the entire SH gene transcription unit. The CVB virus expression vector expresses a heterologous polypeptide, including SARS-CoV-2 spike (S), and / or nucleocapsid (N) and / or membrane (M) proteins, RSV fusion protein (F), or other antigens.

The invention provides a toxoplasma gondii gene deletion strain with an immune protection effect and application of the toxoplasma gondii gene deletion strain, and belongs to the technical field of veterinary parasitology, veterinary immunology and parasite molecular biology. According to the toxoplasma gondii gene deletion strain, a gamma-glutamyl hydrolase gene is deleted. The invention also provides a method for constructing the insect strain. The method comprises the following steps: constructing a circular plasmid pSAG1-Cas9-U6-sgGGH; constructing a repair template containing upstream and downstream homologous arms of the gamma-glutamyl hydrolase gene and a DHFR resistance gene; co-transfecting the annular plasmid and the repair template to a toxoplasma gondii ME49 strain; performing drug screening on pyrimethamine to obtain positive monoclone; and confirming that the GGH gene is completely knocked out through PCR (Polymerase Chain Reaction) detection, sequencing analysis and immunofluorescence detection. The toxoplasma gondii gene deletion strain can provide a remarkable protection effect on toxoplasma gondii infection and is high in safety.

This invention discloses a candidate strain of *R. anatipestifer* double-gene deletion attenuated vaccine, its construction method, and its application. The candidate strain of *R. anatipestifer* double-gene deletion attenuated vaccine is *R. anatipestifer* strain CH-1. B739_RS01935-B739_RS07625 A candidate attenuated live vaccine strain with double gene deletion, deposited at the China Center for Type Culture Collection (CCTCC) on May 22, 2025, with accession number CCTCC NO: M20251080, at Wuhan University, Wuhan, China, has been deposited on that date. The attenuated live strain constructed in this invention showed no significant impact on the weight gain of ducklings after immunization, demonstrating good safety. Furthermore, the protection rate against challenge with the wild-type virulent RACH-1 strain reached 83.3% after immunization, indicating excellent immunoprotective efficacy.

The invention discloses application of a compound AZD5718 in preparation of a medicine for preventing and / or treating cholestatic liver diseases, and belongs to the field of biological medicines. The compound AZD5718 can effectively improve hepatocyte damage and bile metabolism disorder caused by Mdr2 gene deletion, provides solid experimental data support for developing novel drugs for treating cholestatic liver diseases, is expected to provide differentiated therapeutic drug choices for clinic, and has important medical value and social significance.

Contemplated treatments and methods produce substantially increased quantities of memory T-cells and a persistent immune response by subcutaneous and / or subdermal co-administration of (1) a vector comprising a recombinant nucleic acid that encodes a cancer associated epitope, a cancer specific epitope, and / or a neoepitope, (2) an immune stimulating cytokine, and (3) a checkpoint inhibitor. Most typically, the co-administration is performed at substantially the same location, preferably within 1-21 days from each other, and the vector is an adenoviral expression vector, for example, included in a viral particle such as an AdV5 virus with a deletion of the E2b gene.

The invention provides a genetic engineering strain and a construction method thereof, the strain is a target gene deleted strain obtained by knocking out a target gene in a rod-shaped bacterial strain, and the target gene is one of minC and minD genes or a gene combination thereof. According to the present invention, the minC and / or minD gene deletion strain is obtained by knocking out the minC and / or minD gene in the rod-shaped bacterial strain, such that cell division abnormality can be caused, chromosome-free small cells are generated, and the small cells have characteristics of biological activity, no chromosome DNA, and no growth or division propagation. The small cells can generate smaller body immune response, and meanwhile, the LPS modified by the small cells can generate smaller cytotoxic reaction, so that side effects can be greatly reduced when the small cells are applied to human or animal bodies.

Methods are provided for detecting gene deletions and driver mutations using tumor-specific methylation patterns from cell-free DNA and tissue biopsies. The methods exploit the mutual exclusivity between tumor-specific methylation and homozygous gene deletion, enabling detection through absence of expected methylation signals. Applications include detection of MTAP, PTEN, and RB1 deletions, as well as prediction of EGFR single nucleotide (SNV) and small (up to 50 base pair) insertions and deletions (indel) driver mutations, enabling identification of patients eligible for targeted therapies.

The invention relates to the technical field of biological medicines, and discloses a construction method and expression application of an Hcp gene deleted strain of a rahnella aqua KCL-5 strain for fish. The Hcp 0186 gene deletion strain is constructed by using a homologous recombination method, the comparison between the deletion strain and a wild strain is carried out, and the result shows that the deletion of the Hcp 0186 gene has an influence on the growth speed, the pathogenicity of the Hcp 0186 gene to the zebra fish is obviously reduced, the survival rate of the infected zebra fish is increased from 0% to 52%, and the Hcp 0186 gene deletion strain can be used as a fish attenuated live vaccine. A recombinant prokaryotic expression vector pET32a-Hcp and expression and purification of fusion protein of the recombinant prokaryotic expression vector pET32a-Hcp are further constructed, and Hcp 0186 rabbit polyclonal antibody serum is prepared as a primary antibody and can be applied to localization expression analysis of fish tissues infected by the bacterium and detection of WB and IHC. Results prove that the Hcp 0186 gene deletion of the strain provides an attenuated strain vaccine and clinical diagnosis and detection application of infected fish of the attenuated strain vaccine, and a scientific basis can be provided for revealing a molecular pathogenic mechanism of the strain and development and application of a mutant strain of the strain.

The invention discloses a toxoplasma gondii double-gene deletion attenuated vaccine strain as well as a construction method and application thereof. The toxoplasma gondii double-gene deletion attenuated vaccine strain is constructed by deleting a ku80 gene and a CDC14 gene on the basis of a toxoplasma gondii type II PLK strain, and is named as PLK [delta] TgKu80 [delta] TgCDC14 ([delta] CDC14 for short), and experimental results show that the pathogenicity of the strain is remarkably reduced after the CDC14 gene is knocked out. In order to further explore the immune protection effect on toxoplasma gondii acute infection mice, secondary acute infection is carried out on mice immunized with delta CDC14 strains, and the result shows that compared with non-immunized group mice, no immunized mice die within 30 days, and all non-immunized mice die within 13 days. Therefore, the double-gene deletion attenuated vaccine strain has the potential of being used as a vaccine, and an effective technical means is provided for preventing toxoplasma gondii infection.

Provided is an AAV vector capable of expressing a human Mef2c gene in the brain. Specifically, provided are an adeno-associated virus vector capable of expressing a full-length MEF2C protein, and the use thereof. The adeno-associated virus vector can significantly ameliorate the social deficit symptoms of mice with Mef2c gene deletion.

This invention discloses the preparation and application of a substituted heteroaryl ketone compound. The structure of the substituted heteroaryl ketone compound is shown in Formula I, wherein the definitions of each substituent are as described in the specification and claims. The compound of this invention has MAT2A enzyme inhibitory activity and, as a MAT2A inhibitor, can be used to prepare drugs for treating or preventing diseases of MAT2A overexpression and diseases of gene deletion encoding methionine phosphorylase.

The application discloses a colloidal gold test strip for distinguishing between wild toxin infection and vaccine immunization of porcine pleuropneumonia actinobacillus and application. The test strip of the application takes ApxIVA truncated protein with an amino acid sequence shown as SEQ ID NO. 3 as an antigen, the truncated protein can be soluble expressed in E. coli, and the structure and function of the truncated protein are close to those of natural apxIVA. The test strip of the application comprises a sample pad, a colloidal gold pad, an NC membrane, a water absorption filter paper and a bottom plate, the colloidal gold pad is coated with gold-labeled apxIVA truncated protein and gold-labeled chicken IgY antibody, and the C line and the T line of the NC membrane are fixed with goat anti-chicken IgY antibody and apxIVA truncated protein. The test strip only needs 25 muL of pig serum to make detection within 5-10 min, and can distinguish between APP wild strain infection and gene deletion vaccine APP-HB-04M immunized serum samples.

The invention relates to the technical field of biological medicines, and particularly relates to a method for researching the influence of silencing or inhibiting a UBE2G1 gene on the growth of abdominal aortic aneurysm by constructing a UBE2G1 gene function deletion mouse model. Results show that silence or inhibition of UBE2G1 gene expression can inhibit growth of abdominal aortic aneurysm, alleviate destruction of elastic fibers of arterial tissues, reduce levels of inflammatory factors such as TNF-alpha, IL-1beta and IL-6 in a body and inhibit polarization of macrophage M1. According to the invention, a certain theoretical basis is provided in the aspect of treatment of abdominal aortic aneurysm by means of biotechnology, and the UBE2G1 gene (or protein) can be used as a drug target for treatment of abdominal aortic aneurysm.

The invention relates to a CRISPR-Cas12-Cas3 gene editing system. The CRISPR-Cas12-Cas3 gene editing system comprises Cas12 nuclease, a coding gene of the Cas12 nuclease or an expression vector of the Cas12 nuclease; crRNA, a coding gene thereof or an expression vector thereof; and Cas3 nuclease, and a coding gene or an expression vector thereof. The system is characterized in that Cas12 only cuts a non-target chain to generate a specific single-chain gap, and accurate starting of Cas3 process excision activity is realized through direct compounding with Cas3, so that directional large fragment deletion is induced under the condition that double-chain breakage is not generated. Compared with a traditional I-type CRISPR system depending on a Cascade complex, the system has the advantages that the components are obviously simplified, and the operation is more convenient. Compared with an editor composed of single Cas12, the method can be used for deleting long-fragment genes and other modifications.

This study describes the construction, identification, and application of a pseudorabies virus (PRV) triple-gene deletion vaccine strain (gI / gE / TK). Based on the JS-2012-ΔgI / gE double-gene deletion strain, the TK virulence gene was further deleted using CRISPR technology. Its pathogenicity was evaluated in KM mice and piglets, and its immunoprotective efficacy was verified in piglets. This provides theoretical support for the clinical prevention and control of pseudorabies; establishes experimental models in mice and pigs to study the immunoprotective efficacy of the triple-gene deletion strain; and prepares for the subsequent development and evaluation of vaccines using PRV strains as vectors.

The invention belongs to the technical field of veterinary vaccines, and particularly relates to an orf virus ORF114 or ORF117 gene deleted strain as well as a preparation method and application thereof. The orf virus ORF114 gene deleted strain is obtained by deleting ORF114 on the basis of an orf virus wild strain, and the orf virus ORF117 gene deleted strain is obtained by deleting ORF117 on the basis of the orf virus wild strain. According to the preparation method, on the basis of an ORFV-CF15 strain (ORFV 2015 strain), ORF114 and ORF117 genes of the ORFV-CF15 strain are deleted by using a gene recombination combined Cre-LoxP system, and two orf gene deleted strains are constructed and screened, and the orf virus ORF114 or ORF117 gene deleted strains have the characteristics of low toxicity, good proliferation and enhancement of Th1 type immune response, and can be used as orf gene engineering vaccine candidate strains.

The present application relates to a kind of carp herpesvirus II type ORF150 gene deletion strain and its preparation method and application, belong to aquatic animal disease prevention and control technical field.The present application carp herpesvirus II type ORF150 gene deletion strain preservation number is CCTCC NO:V202603, is preserved in China typical culture preservation center, and is named carp herpesvirus 2 type CyHV-2-SS24-Δ150-GFP Cyvirus cyprinidallo2 The virulence of the present application carp herpesvirus II type ORF150 gene deletion strain is significantly weakened, but still retains good immunogenicity, can induce the immune fish body to produce immune protection to carp herpesvirus II type.ORF Therefore, the present application carp herpesvirus II type ORF150 gene deletion strain can be used as live attenuated vaccine to carp herpesvirus II type, prevent koi and its variety in aquaculture from being infected by carp herpesvirus II type and lead to hematopoietic organ necrosis disease.

The application discloses a gene prdR for regulating myxobacteria predation and a protein coded by the gene, and belongs to the technical field of biotechnology. The mutant DK10 with significantly improved predation capacity is obtained by using the strategy of adaptive evolution; genetic variation sites of the mutant DK10 are analyzed by using the bacterial genome resequencing technology, and functions of the genetic variation sites are researched by using the gene knockout technology, and it is found that the gene deletion of MXAN_2902 (prdR, the nucleotide sequence is shown as SEQ ID NO. 1) significantly enhances the predation capacity of Myxococcus xanthus. The nucleic acid sequence and the amino acid sequence of the transcriptional activator PrdR for regulating the predation of Myxococcus xanthus are disclosed, and the functional strain of Myxococcus xanthus capable of efficiently predating Salmonella enteritidis can be developed by using the prdR gene, and a new strategy is provided for the prevention and control of drug-resistant HVPG pathogenic bacteria.

The invention belongs to the technical field of biological detection, and discloses a method for simultaneously detecting large fragment deletion of ACE (Angiotensin Converting Enzyme) and CYP2D6 genes. The kit provided by the invention can simultaneously amplify a plurality of target fragments (such as CYP2D6 gene deletion long fragments and ACE gene deletion short fragments) with obvious size difference under the same system, so that the experimental operation steps are reduced by half, and the detection time is obviously shortened; the reagent cost is saved, and the use amount of an electrophoresis reagent is reduced by half; operation links are reduced, and the risk of sample confusion is reduced.

The invention belongs to the technical field of gene engineering, and particularly relates to aureobasidium pullulans with high yield of pullulan and application of the aureobasidium pullulans. On the basis of aureobasidium pullulans M233-20, an isopullulanase gene A9187 gene in a genome of the aureobasidium pullulans M233-20 is knocked out based on a homologous recombination technology, and through polysaccharide fermentation test detection, an isopullulanase gene deletion mutant strain aureobasidium pullulans delta A9187-1 with the pullulan polysaccharide molecular weight improved and the yield not reduced is obtained. The weight-average molecular weight of the pullulan produced by the recombinant strain is 6.5 * 10 < 5 > Da, which is 2.6 times that of the original wild strain (2.46 * 10 < 5 >), and the yield of the pullulan is increased from 147.33 g / L to 156 g / L, which is increased by 5.88%.

The present application relates to bovine tuberous skin disease virus, in particular, to bovine tuberous skin disease virus ORF145 gene deletion strain and its application. The gene deletion strain is characterized in that it is constructed by deleting ORF145 gene from bovine tuberous skin disease virus virulent strain LSDV XJ201901. Compared with the parent strain, the replication level of the constructed deletion strain rLSDVΔ145 in in vitro cells is equivalent to that of the parent strain, indicating that the gene deletion does not affect the in vitro proliferation ability of the virus. In addition, after rLSDVΔ145 infects MDBK cells, it can significantly reduce the mRNA expression level of pro-inflammatory factors IL-1beta and IL-6, while not interfering with the expression of IFNbeta mRNA. Further transcriptomic analysis shows that the deletion strain significantly reduces virulence and pathogenicity on the basis of maintaining good immunogenicity; it not only loses the inhibition ability to the innate immune pathway, but also can effectively activate the adaptive immune response, and significantly reduce the risk of inflammation and tissue damage, showing significant potential as a safe and efficient attenuated live vaccine.

The invention discloses an application of mitochondrial topoisomerase I or a coding gene thereof, relates to the technical field of biological medicines, and particularly provides an application of the mitochondrial topoisomerase I or the coding gene thereof as a therapeutic target in screening or preparing a medicine for treating Alzheimer's disease. The action mechanism of the mitochondrial topoisomerase I in the Alzheimer's disease is fully explored, it is found that deletion of the coding gene of the mitochondrial topoisomerase I can cause increase of APP and A beta levels and finally cause learning and memory impairment similar to the Alzheimer's disease, and the mitochondrial topoisomerase I can be used as a potential target for treatment of the Alzheimer's disease and can be used for treating the Alzheimer's disease. The overexpressed mitochondrial topoisomerase I can significantly reduce APP and A beta levels and treat the Alzheimer's disease.

The invention provides a bovine nodular skin disease virus double-gene deletion strain as well as a vaccine and application thereof, and belongs to the technical field of biological medicines. The bovine nodular skin disease virus (LSDV) double-gene-deleted strain is characterized in that the virus strain is named as rLSDV-DoubMut, the preservation number of the virus strain is CGMCC NO: 46988, the preservation unit is China General Microbiological Culture Collection Center, the preservation time is December 23, 2025, the bovine nodular skin disease virus single-gene-deleted strain LSDV-005 is used as a parent strain, the bovine nodular skin disease virus single-gene-deleted strain LSDV-005 is used as a parent strain, the bovine nodular skin disease virus single-gene-deleted strain LSDV-005 is used as a parent strain, and the bovine nodular skin disease virus single-gene-deleted strain LSDV-005 is used as a parent strain. The gene is constructed by knocking out an ORF131 gene. The rLSDV-DoubMut has the advantages of genetic stability, high safety, strong immunogenicity and the like, and immune animals and wild virus infected animals can be distinguished through a 131 protein-based detection method.

The application discloses an ELISA antibody detection kit for identifying Brucella gene deletion live vaccine (M5-90△26 strain) and wild strains and application. The kit comprises enzyme-linked reaction plate 1 and enzyme-linked reaction plate 2. The enzyme-linked reaction plate 1 is coated with LPS extracted from the Brucella gene deletion live vaccine (M5-90△26 strain), and the enzyme-linked reaction plate 2 is coated with a Brucella BP26 antigen epitope polypeptide combination composed of polypeptides with amino acid sequences shown in SEQ ID NO:1-2. The application is suitable for goats and sheep inoculated with the Brucella gene deletion live vaccine (M5-90△26 strain), can effectively distinguish the antibody produced by the Brucella gene deletion live vaccine (M5-90△26 strain) and the antibody produced by wild strain infection, thereby realizing identification and detection, being favorable for prevention and control of brucellosis and optimization of a vaccination strategy, and providing technical support for healthy and sustainable development of animal husbandry.

The present invention relates to a pharmaceutical composition comprising a Runx3 gene or protein as an active ingredient for prevention or treatment of K-Ras mutant lung cancer. Specifically, Runx3 gene-deleted, K-Ras gene-activated lung cancer mice established in the present invention were found to be completely cured without lung cancer recurrence likelihood when restoring the Runx3 gene, compared to the conventional approach of inhibiting the activated cancer gene. Thus, the composition comprising Runx3 protein, a polynucleotide coding therefor, a vector carrying the polynucleotide, or a virus or cell transformed with the vector as an active ingredient according to the present invention can be advantageously used as a composition for prevention or treatment of K-Ras mutant lung cancer.

The application discloses a kind of establishment and application of flavivirus replication-dependent RNA recombination experimental system, belong to the field of biotechnology.The RNA recombination system includes two components: tanbusu virus E gene deletion subgenomic replicon CQW1-ΔE, and the defective virus genome CQW1-ΔNS1 or MM1775-ΔNS1 missing partial NS1 gene sequence.The two components cannot produce progeny virus alone, but after co-transfection, due to RNA recombination, a large number of recombinant progeny viruses can be produced within a few days after transfection, the recombination efficiency is extremely high, and continuous passage is not required, greatly shortening the construction cycle and saving production costs;At the same time, the progeny virus can form plaques on cells, and the efficiency of RNA recombination can be quantitatively measured by plaque counting, and the key factors affecting tanbusu virus RNA recombination can be analyzed.

This invention belongs to the field of bioengineering technology, specifically relating to the construction of a double-gene-deleted attenuated African swine fever virus strain and its application as a vaccine. This invention combines the deletion of the MGF505-7R and I267L genes in the ASFV CN / GS 2018 virus, reducing the virulence of the parent strain and obtaining an attenuated African swine fever vaccine strain. The attenuated African swine fever vaccine strain completely attenuates pigs after immunization, with 100% survival rate, and provides immune protection against challenge with the virulent ASFV CN / GS / 2018 strain. It can serve as a safe and effective candidate vaccine for the prevention and control of African swine fever, possessing significant social value.

The application belongs to the field of genetic engineering and medical engineering, and discloses virK Application of gene in regulation of Klebsiella pneumoniae virulence. The application finds that the expression level of the gene is significantly increased in polymyxin-resistant mutant strains through transcriptome analysis, virK Further research shows that the expression of the gene is regulated by the PhoP / PhoQ two-component regulatory system. The application constructs virK Gene deletion mutant strains and complementary strains, and compares the virulence difference of the strains in an animal infection model, finds that virK The virulence of the deletion strain is significantly reduced, and the complementary strain can restore the virulence phenotype, indicating that virK The gene plays an important role in the regulation of Klebsiella pneumoniae virulence. The application first finds that PhoP can regulate virK Gene expression, and affects the virulence phenotype of Klebsiella pneumoniae through the regulation pathway, thereby revealing a new virulence regulation mechanism, and providing a theoretical basis for subsequent targeted intervention.

The invention relates to the technical field of biological genes, in particular to a gene directed editing system applied to mycoplasma bovis, which is an editing system for expressing a combination of a single plasmid of GP35 single-chain annealing protein and a targeting fragment ssDNA (single-stranded deoxyribonucleic acid), and comprises an expression plasmid of a GP35 gene and the ssDNA of the targeting fragment. The invention relates to a gene directed editing method applied to mycoplasma bovis. The gene directed editing method comprises the following steps: constructing a mycoplasma bovis strain for expressing GP35 single-chain annealed protein, constructing an ssDNA single chain of a targeting fragment, and performing gene editing on a target gene to obtain a pdhC gene deleted strain. According to the invention, a KanR gene is successfully inserted at the 158bp position of a pdhC gene coding region of a mycoplasma bovis PG45 strain, so that a mycoplasma bovis pdhC gene oriented deletion strain is obtained. According to the invention, the metabolism-related gene directed deletion strain M. bovis PG45 [delta] pdhC is successfully constructed, and the pdhC protein is characterized to have the ability of regulating the growth rate of mycoplasma bovis and maintaining colonial morphology.