100 results about "Linker peptide" patented technology

The invention discloses an immunogenic composition containing an adjuvant as well as a preparation method and application of the immunogenic composition. The immunogenic composition comprises self-assembled gE virus-like nanoparticles, an immunopotentiator, namely, saponin QS-21, and a neutral liposome, the self-assembled gE virus-like nanoparticles are formed by polymerizing and assembling monomers; the monomers include VZV gE, a linker peptide (SGS), and a VZV gI polypeptide containing a Th epitope. The immunogenic composition can be applied to varicella-zoster virus vaccines, and solves the technical problems of weak gE immunogenicity and serious vaccine side reaction in vaccines prepared in the prior art. The immunogenicity of the vaccine is equivalent to that of the Xinanlii, and the use of an immunopotentiator in the vaccine can be reduced, so that the clinical side reaction of the vaccine is lower; in addition, the vaccine can induce a gI specific antibody and gI specific CMI reaction, and the effectiveness of the vaccine can be further improved. In short, the immunogenic composition has good clinical application potential.

The invention discloses a fusion protein taking peptide-N-glycosidase as an active component as well as a preparation method and application of the fusion protein, and belongs to the technical field of biological medicines. The fusion protein comprises: (a) peptide-N-glycosidase or a catalytically active fragment thereof; (b) an immunoglobulin Fc domain, or a combination of a tumor or immune cell antigen binding domain and an immunoglobulin Fc domain; (c) a linker peptide; wherein the form of the tumor or immune cell antigen binding domain is Fab, scFv or VHH; the peptide-N-glycosidase or the catalytic activity fragment of the peptide-N-glycosidase is connected with the Fc structural domain of the immunoglobulin through the connecting peptide; the immunoglobulin Fc domain mediates the fusion protein to form a homodimer or a heterodimer. According to the invention, the synergistic function of targeted binding and local deglycosylation of the target molecule is realized, so that the immunosuppressive activity of the target molecule is interfered, and the anti-tumor immune response is enhanced.

The invention discloses an immunogenic composition containing a composite adjuvant as well as a preparation method and application of the immunogenic composition. The immunogenic composition comprises a gE-gI fusion protein, an immunopotentiator, namely, saponin QS-21, and a neutral liposome, the gE-gI fusion protein comprises a VZV gE, a connecting peptide and a VZV gI. The immunogenic composition provided by the invention only contains one immunopotentiator, can be applied to VZV vaccines, and solves the problems of relatively weak gE immunogenicity and relatively large clinical side reaction of the vaccines prepared in the prior art. The immunogenicity of the vaccine is equivalent to that of the Xinanlii, but the vaccine contains fewer immunopotentiators and has lower clinical side effects; in addition, the vaccine can also induce a gI specific antibody and gI specific CMI reaction, which is beneficial to further improvement of the effectiveness of the vaccine. In short, the immunogenic composition has good clinical application potential.

This invention belongs to the field of biomedical technology, specifically relating to a colorectal cancer antibody and its applications. The antibody is composed of a camel-derived VHH-3 single-domain antibody and a membrane-penetrating peptide TAT fused together via a flexible linker peptide (GGGGS)3, and its amino acid sequence is shown in SEQ ID NO:9. This invention uses phage display technology to screen for high-affinity VHH-3 (KD=0.9524 nM) and further constructs the membrane-penetrating nanobody TAT-VHH-3, achieving soluble and efficient preparation using a prokaryotic expression system. Experiments confirm that TAT-VHH-3 can significantly inhibit the proliferation (CCK-8 assay) and migration (scratch assay) of colorectal cancer Caco-2 cells in a concentration-dependent manner. The nanobody of this invention has advantages such as small molecular weight (approximately 16.1 kDa), strong penetrability, and high stability, providing a novel tool for tumor therapy targeting CaMKⅡα.

This invention discloses a fusion protein targeting the urokinase-type plasminogen activator receptor and its application in the field of anti-aging. The fusion protein is composed of a hepatocyte growth factor active domain and a humanized anti-uPAR single-domain antibody linked by a flexible linker peptide, and its specific amino acid sequence is SEQ ID NO:3. This fusion protein can specifically bind to uPAR, which is highly expressed on the surface of senescent cells, with intramolar affinity, achieving targeted delivery of the hepatocyte growth factor active domain. In vitro experiments have demonstrated that this protein can significantly reverse the aging phenotype of human fibroblasts, effectively reduce aging-related β-galactosidase activity, p16INK4a protein expression, and interleukin-6 secretion, and promote cell proliferation. In a rapidly aging mouse model, this protein can systematically improve age-related physiological functional decline. The fusion protein of this invention achieves specific targeting and efficient treatment of senescent cells, providing a new solution for the development of anti-aging drugs.

This invention belongs to the fields of biotechnology and genetic engineering, and relates to a dual-enzyme fusion protein resistant to hydrogen peroxide inhibition, a polynucleotide, an expression vector, and its applications. The dual-enzyme fusion protein is composed of a glutamate oxidase mutant, a catalase mutant, and a linker peptide; the amino acid sequences of the glutamate oxidase mutant and the catalase mutant are shown in SEQ ID NO. 2 and 4, respectively, in the sequence listing. This invention improves the performance of single enzymes through enzyme molecule modification, achieves spatial synergy through fusion protein design, and enables industrial application through a continuous reaction process; it fundamentally solves the problem of hydrogen peroxide's inhibition of glutamate oxidase products; and the fusion expression simultaneously improves the stability and reusability of the dual enzymes.

The invention relates to the technical field of biological medicine, and discloses a targeting molecule for inhibiting generation of PD-L1 and giant cells mediated by a tumor exosome HMGB1 and application of the targeting molecule, the targeting molecule comprises a first binding unit, a second binding unit and a flexible connecting peptide for connecting the first binding unit and the second binding unit; the amino acid sequence of the first binding unit is Asp-Gly-Arg-Tyr-Phe-Leu-Ser-Pro-Asn-Lys, and the first binding unit can be specifically bound with a binding boundary of a C-terminal acid tail of HMGB1 on the surface of a tumor exosome and RAGE; the amino acid sequence of the second binding unit is Trp-His-Glu-Val-Met-Ala-Gln-Ile-Arg-Ser, and the second binding unit can be specifically bound with an extracellular structural domain of PD-L1 on the surface of the macrophage; the amino acid sequence of the flexible connecting peptide is Gly-Gly-Ser-Gly, and the amino acid sequence of the flexible connecting peptide is Gly-Gly-Ser-Gly. In order to achieve the purpose of specifically inhibiting PD-L1 expression mediated by tumor exosome HMGB1 and giant cell generation, a targeting molecule containing a bispecific binding unit is designed, a first binding unit is specifically bound with a specific binding interface of the tumor exosome surface HMGB1, and a second binding unit is specifically bound with an extracellular structural domain of PD-L1 on the macrophage surface; therefore, the purpose is achieved.

The present disclosure provides a polypeptide fragment comprising a polypeptide of a modified hemagglutinin protein, wherein said modified hemagglutinin protein comprises a linker peptide replacing the polypeptide in the cytoplasmic domain of hemagglutinin protein, wherein the hemagglutinin protein is obtained from at least one seasonal strain of influenza virus, wherein said polypeptide of the modified hemagglutinin protein is having at least 80%, or at least 90%, or at least 95%, or at least 97% sequence identity to at least one sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, and SEQ ID NO: 30.

A recombinant hemoglobin, a nucleic acid encoding the recombinant hemoglobin, and a preparation method therefor are provided to address the current problems of complex processes, high production costs, and low yields that exist for improving a hemoglobin having a stable tetrameric structure. The recombinant hemoglobin comprises: two or more units of recombinant hemoglobins, the units of recombinant hemoglobins each comprise four polypeptide chains, and the polypeptide chains are two α chains and two β chains. The amino acid sequences of the four polypeptide chains of each unit of recombinant hemoglobin are linked by means of intra-unit linker peptides to form the unit of recombinant hemoglobin, and two or more of the units are linked by means of inter-unit linker peptides.

The present invention discloses a subunit vaccine against chicken infectious anemia virus, belonging to the technical field of animal disease vaccines. The present invention provides a subunit vaccine against chicken infectious anemia virus, and the active ingredient is a recombinant fusion protein of the B cell epitope of chicken infectious anemia virus VP1 protein and Salmonella typhimurium flagellin. The B cell epitope of chicken infectious anemia virus VP1 protein is obtained by connecting the B cell antigen epitopes contained in chicken infectious anemia virus VP1 protein through a linker peptide. The Salmonella typhimurium flagellin is obtained by deleting the hypervariable region of Salmonella typhimurium flagellin FliC. After the fusion expression protein of the present invention is administered to 1-day-old SPF chickens, it can induce the production of specific IgG antibodies, and after 28 days of immunization, the immunized chicken flock can resist the challenge of the virulent strain of chicken infectious anemia virus, and 70% of the challenged chicken flock is protected from disease. The present invention has great potential for clinical prevention and control of chicken infectious anemia virus infection.

The invention provides an N-deacetylase / N-sulfotransferase and an application of the N-deacetylase / N-sulfotransferase. According to the invention, systematic stability design and surface electrostatic optimization are carried out on the N-deacetylation structural domain of NDST, and multiple engineering strategies such as structural domain fusion and linker peptide optimization are combined to synergistically improve the specific activity, substrate affinity and bifunctional catalytic synergy of enzyme. Experimental results show that the specific enzyme activity of the modified NDST mutant is obviously higher than that of natural enzyme while the difunctional catalytic capability is maintained.

Provided are a preparation method for a fusion polypeptide, and the use thereof. The fusion polypeptide is formed by directly linking SEQ ID NOs: 1-8 (referred to as O peptide) or a homologous sequence thereof, and SEQ ID NOs: 9-17 (referred to as G peptide) or a homologous sequence thereof, and a functional domain via a linker peptide (linker). The fusion polypeptide is formed by directly linking, in sequence from the N-terminus to the C-terminus, a G peptide or a homologous sequence thereof, an O peptide or a homologous sequence thereof, and a functional domain via a linker peptide (linker) (rigid or flexible); and the fusion polypeptide is formed by directly linking, in sequence from the N-terminus to the C-terminus, an O peptide or a homologous sequence thereof, a G peptide or a homologous sequence thereof, and a functional domain via a linker peptide (linker) (rigid or flexible). The fusion polypeptide has significant agonist activity against GPR158 and / or GPRC6A and / or GPR37, and also has significant antagonist activity against GPR1. The fusion polypeptide can be used in the preparation of drugs for treating alopecia, acne, dermatitis and other related diseases.

The invention discloses an immunogenic composition containing gE virus-like nanoparticles as well as a preparation method and application of the immunogenic composition. The immunogenic composition comprises gE virus-like nanoparticles, an immunopotentiator, namely, saponin QS-21, and a neutral liposome, the gE virus-like nanoparticles comprise VZV gE, a linker peptide (SGS) and a VZV gI polypeptide containing a Th epitope. The immunogenic composition provided by the invention can be applied to VZV vaccines, and solves the technical problems of weak gE immunogenicity and serious vaccine side reaction in vaccines prepared in the prior art. The immunogenicity of the vaccine is better than that of Xinanliei, the use of an immunopotentiator is reduced, and the clinical side reaction is lower. In addition, the vaccine can also induce an obvious gI specific antibody, which is beneficial for further improving the effectiveness of the vaccine. In short, the immunogenic composition provided by the invention has good clinical application potential.

The present invention provides a composite molecule, a nucleic acid, a vector, a host cell, and a pharmaceutical composition, and uses of the composite molecule, the nucleic acid, the vector, the host cell, and the pharmaceutical composition in preparation of drugs for treating cancers. The composite molecule comprises an anti-tumor antibody domain, a linker, and pro-IL-15; the anti-tumor antibody domain is linked to the pro-IL-15 by means of the linker; the anti-tumor antibody domain is a complete antibody against an immune checkpoint molecule, a tumor antigen molecule or an immune activation molecule, or a nano antibody or an antigen binding fragment thereof; the linker is a polypeptide linker or a non-peptide linker; the pro-IL-15 is a fusion protein comprising IL-15, an IL-15Rα sushi domain, and a linker peptide, and optionally comprising an IL-15Rβ extracellular domain; and the IL-15Rβ extracellular domain, the IL-15, and the IL-15Rα sushi domain are linked by means of the linker peptide.

The application provides an engineered exosome loaded with a CD63 transmembrane domain-matrix metalloproteinase fusion protein and a preparation method and application thereof. The engineered exosome is secreted by a genetically engineered mesenchymal stem cell, has a CD63 derived transmembrane domain anchored on the membrane, and has a matrix metalloproteinase (MMP) loaded on the inner side of the membrane. The fusion protein comprises, from N-terminus to C-terminus, a fourth transmembrane domain and a C-terminal cytoplasmic tail of a human CD63 protein, a flexible linker peptide, and a human MMP without a natural signal peptide. The application realizes efficient and directional loading of MMPs by using a natural biological generation path of the exosome, shields the inhibition of MMPs by metalloproteinase tissue inhibitors in a scar tissue by using the membrane of the exosome, realizes specific activation of MMPs in a target cell, degrades abnormally deposited collagen, adjusts the ratio of type I and type III collagens, and plays an anti-fibrosis and anti-scar formation role. The application also provides a preparation method of the engineered exosome and application thereof in preparation of a medicine for preventing or treating pathological scars.

The application discloses a SARS-CoV-2 epitope type vaccine multi-epitope combination and application, and belongs to the technical field of coronavirus vaccine research and development.The first aspect of the application relates to a fusion protein, which comprises in sequence: (a) a SARS-CoV-2 spike protein receptor binding domain or a functional fragment thereof; (b) a T cell epitope domain, comprising: a CTL epitope cluster, the CTL epitope cluster comprising at least one CD8+ T cell epitope polypeptide selected from SEQ ID NO: 1-15; and (c) an immunoglobulin Fc domain.The application adopts a tandem strategy of immunodominant epitopes + conserved epitopes, predicts high-affinity T cell epitopes by computational biology methods, evaluates the HLA restriction in different populations, introduces a flexible linker peptide for optimization design, evaluates the immune effect difference of different combinations through in vitro and animal models, analyzes the synergistic or competitive relationship between epitopes, and optimizes the vaccine design.Through systematic comparison of the immunological effect difference of different epitope combinations and the adaptability to various vaccine platforms, the application establishes an optimized safe, efficient, broad-spectrum and long-acting multi-epitope vaccine design strategy, and has significant application value and important transformation value.

The invention discloses a proantibody drug conjugate capable of being activated by multiple proteases as well as a preparation method and application of the proantibody drug conjugate. The proantibody drug conjugate is named as PDC-PC1, a section of connecting peptide capable of being split by protease is added to each of amino terminals of two light chains of HcHAb18, on this basis, masking peptides used for preventing the antibody from being combined with an antigen are fused to the connecting peptides to form the proantibody PC1, a small-molecule tubulin inhibitor MMAE is cross-linked to an inter-chain disulfide bond of the PC1 in a fixed-point mode, and the proantibody drug conjugate is obtained. Therefore, the proantibody drug conjugate PDC-PC1 is formed. The new-generation PDC drug PDC-PC1 provided by the invention endows parent antibody with dual characteristics of conditional selective targeting combination and tumor microenvironment (TME) response delivery treatment, the targeting selectivity is remarkable, the specificity is stronger, the cross toxic and side effects are effectively reduced, and the accurate targeting curative effect is further improved through the introduction of MMAE fixed-point crosslinking.

The present application belongs to the technical field of biomedicine, and relates to an in vivo self-assembling system targeting the central nervous system for treating diabetes. The present application provides an in vivo self-assembling system targeting the central nervous system. The in vivo self-assembling system targeting the central nervous system is a recombinant plasmid expressing a nucleic acid molecule, wherein the nucleic acid molecule encodes a fibroblast growth factor-based fusion protein, and the fibroblast growth factor-based fusion protein comprises a propeptide, a peptide targeting the central nervous system, a linker peptide, and a fibroblast growth factor variant having an amino acid sequence as set forth in SEQ ID NO.1, which are sequentially linked. The in vivo self-assembling system targeting the central nervous system can cross the blood-brain barrier and specifically reach the central nervous system via routes other than intracranial injection, such as subcutaneous injection and intravenous injection. The system exerts a long-lasting blood glucose-lowering effect, without causing adverse reactions, thereby retaining the anti-diabetic activity of fibroblast growth factors and avoiding the tumorigenic risks thereof.

A tumor vaccine for treating esophageal squamous cell carcinoma and other cancers, and a composition thereof. Specifically, provided is a polypeptide, which contains one or more antigen fragments selected from: ACTL8, BRDT, FOXI3, GNGT1, SMC1B, PLAC1, MAGEA1, MAGEA3, MAGEA4, MAGEA6, MAGEA10 and MAGEA11, wherein the one or more antigen fragments are linked via a linker peptide, and the antigen fragments contain one or more antigenic epitope peptides. Furthermore, provided are a linear epitope peptide, a nucleic acid encoding the polypeptide and the linear epitope peptide, and the use of the polypeptide or the linear epitope peptide in the preparation of a drug for preventing or treating cancers such as esophageal squamous cell carcinoma.

The invention relates to the technical field of biology, in particular to a method for regulating and controlling the methylation level of a plant genome DNA specific region by using a Cas12i system. The invention provides a fusion protein. The fusion protein sequentially comprises a first nuclear localization signal peptide, a methylation modification structural domain, a connecting peptide, a nuclease activity-free Cas12i protein and a second nuclear localization signal peptide from an N terminal to a C terminal, the methylation modification structural domain is OsSUVH2 protein capable of up-regulating the methylation level or a functional active fragment of the OsSUVH2 protein; the amino acid sequence of the OsSUVH2 protein is as shown in SEQ ID NO: 1; the amino acid sequence of the nuclease activity-free Cas12i protein is as shown in SEQ ID NO: 3. The invention also provides a CRISPR-dCas12i system constructed on the basis of the fusion protein. According to the CRISPR-dCas12i system, the methylation modification efficiency of the plant genome DNA is remarkably improved.

The invention relates to the technical field of agriculture, in particular to an efficient ABE base editing tool based on Cas12i3 and application of the efficient ABE base editing tool. The Cas12i3-based efficient ABE base editing tool provided by the invention comprises a protein expression cassette and an RNA (Ribonucleic Acid) expression cassette, the protein expression cassette comprises a promoter, a 2 * BP NLS nuclear localization signal fragment, a 2 * adenine deaminase TadA8e, a connecting peptide, a Cas12i3 notch enzyme fragment and a terminator, the RNA expression cassette comprises a promoter, a crRNA sequence and a terminator; wherein the crRNA sequence is composed of a DR sequence and a target specific spacer sequence. The tool realizes efficient and specific single base substitution of A-to-G in a rice genome by utilizing the targeted binding characteristic of Cas12i3 and the efficient deamination activity of 2 * TadA8e, has the advantages of high editing efficiency, low off-target rate, wide application range and the like, provides an efficient and accurate technical means for plant functional genome research and molecular breeding, and has a wide application prospect. The creation of excellent rice varieties can be accelerated.

The invention discloses a CAR-T cell modified by an interleukin 15 receptor alpha mutant and application of the CAR-T cell, and particularly relates to a gene engineering medicine. The CAR-T cell is integrated with a multi-gene expression unit through an SB100X transposon system, wherein the multi-gene expression unit comprises opti-mIL-15 (T62G / L55F), opti-mIL-15R alpha-Sushi (Q199E / D203A), a GPI anchoring sequence, a (G4S) 3 flexible connecting peptide, a targeted CAR gene and an iC9 safety switch, and a membrane binding type IL-15 / IL-15R alpha compound supported by an autocrine signal is formed. The affinity and stability of IL-15 signals are enhanced through mutants, efficient integration and co-expression are achieved through non-viral vectors, the in-vivo durability, amplification capacity and anti-tumor activity of CAR-T cells are remarkably improved, and meanwhile a cell factor local delivery and induction type safety switch system is combined through a membrane.

This invention discloses a high-efficiency protein expression system, its construction method, and its applications. The system includes a heterozygous promoter activator and a heterozygous promoter. The heterozygous promoter activator consists of the DNA-binding protein TetR, a linker peptide, and the transcription activator Mit1-Δ60-96. The heterozygous promoter consists of the protein-binding sequence TetO, a spacer sequence, and a basal promoter. The linker peptide is (GGGGS)×2, the spacer sequence is TCGCGCGC, and the basal promoter is P. AOX1 The core promoter of this invention. In the absence of a heterozygous promoter activator, the target protein gene initiated by the heterozygous promoter is expressed very weakly; in the presence of a heterozygous promoter activator, the target protein gene is expressed efficiently. This invention's system has good applicability and scalability, and the expression intensity of various target proteins, including xylanase, phytase, and glucosidase, is significantly higher than that of commonly used P. AOX1 Promoter.

This invention relates to the field of biomedical technology, providing a rabbit hemorrhagic disease virus (RHDV) type 2 fusion antigen protein and its applications. The fusion antigen protein comprises the RHDV2 VP60 protein sequence and an immunomodulatory CRM197 protein functional fragment, fused together via a linker peptide, and expressed and purified in an insect cell expression system. This invention improves the immunogenicity of the antigen protein by fusing the major capsid protein VP60 of RHDV2 with the immunomodulatory fragment of CRM197. Rabbit immunization experiments verified that the fusion antigen protein can induce high-titer specific antibodies, with serum antibody titers reaching 1:12800 and above, demonstrating good immunization effects. The fusion antigen protein of this invention can be used to prepare a vaccine for the prevention of RHDV2 infection, providing a new technical solution for the prevention and control of RHDV2 disease.

The present invention belongs to a biopharmaceutical technology, and specifically relates to a fusion polypeptide and a derivative thereof, and the use thereof in the preparation of a drug for treating alopecia, acne, dermatitis and other related diseases. Disclosed is a fusion polypeptide, wherein the fusion polypeptide sequentially consists of an O peptide or a derivative peptide thereof, and an I peptide or a derivative peptide thereof from the N-terminus to the C-terminus, and the two structural functional domains are connected via a linker peptide linker or directly; or the fusion polypeptide sequentially consists of an I peptide or a derivative peptide thereof, and an O peptide or a derivative peptide thereof from the N-terminus to the C-terminus, and the two structural functional domains are directly connected via a linker peptide. The provided fusion polypeptide can simultaneously activate GPR158 and / or GPRC6A and / or GPR37 pathways, and simultaneously activate the integrin receptor pathway, has the remarkable advantages of high activity in promoting hair growth, rapid onset of action and long action duration in regulating hormone, thereby providing a new drug for treating alopecia, acne, dermatitis and other related diseases.

The present disclosure provides a recombinant Escherichia coli for preparing soluble EC-SOD and its application, relating to the field of bioengineering technology. In the present disclosure, the genes of SOD and KGF2 are ligated using a coding sequence of a linker peptide containing a protease cleavage site and cloned into a pET28a expression vector. The pET28a expression vector is transformed into competent Escherichia coli BL21(DE3) cells to construct the recombinant Escherichia coli. The obtained recombinant Escherichia coli can solve the problem that EC-SOD forms inactive inclusion bodies during expression in Escherichia coli. It is applicable to the preparation of soluble EC-SOD.

The invention discloses an immunogenic composition as well as a preparation method and application thereof. The immunogenic composition comprises self-assembled gE nanoparticles, an immunopotentiator, namely, saponin QS-21, and a neutral liposome, the self-assembled gE nanoparticles are formed by polymerizing and assembling a plurality of monomers, and the monomers comprise VZV gE, a linker peptide (SGS) and VZV gI polypeptide containing Th epitopes. The immunogenic composition can be applied to VZV vaccines, and solves the technical problems of weak gE immunogenicity and serious vaccine side reaction in vaccines prepared in the prior art. The immunogenicity of the vaccine is equivalent to that of Xinanliei, and the use (variety and dosage) of an immunopotentiator can be reduced, so that the clinical side reaction of the vaccine is lower; in addition, the vaccine can induce a high-level gI specific CMI reaction, which is beneficial to further improvement of the effectiveness of the vaccine. In short, the immunogenic composition has good clinical application potential.

A DNA molecule for targeted degradation of a target protein and the use thereof. The DNA molecule comprises at least one group of D-PROTAC units, wherein each group of D-PROTAC units comprises at least one first DNA segment encoding a ubiquitin ligase-targeting peptide, at least one second DNA segment encoding a target protein-targeting peptide, and a third DNA segment encoding a linker peptide which is optionally arranged between the adjacent first DNA segment and second DNA segment. A gene therapy-specific PROTAC molecular model is successfully constructed, which proves the great potential of gene therapy in the research, development and application of new anticancer PROTAC drugs, innovates the mode of action of PROTAC technique, and extends new therapeutic application scenarios for gene therapy.

The invention discloses a polypeptide targeting lysosome, a lysosome fluorescent probe and a kit, and belongs to the technical field of biology. The polypeptide of the targeted lysosome sequentially comprises a part A, a part B, a part C and a part D from the N end to the C end, the part A is a cell penetrating peptide sequence, the part B is a lysosome targeted positioning sequence, the part C is a connecting peptide sequence, and the part D is a fluorescent protein sequence. The polypeptide can rapidly enter cells and target and locate in lysosome, has good biological safety and stability, can be used as a lysosome fluorescent probe, is suitable for fluorescence imaging of lysosome in different living cells, and has specificity for lysosome staining. Therefore, a lysosome polypeptide probe kit can be developed, and accurate lysosome cell device positioning and convenient application are provided for scientific experimental research.

A C-terminal truncated alginate lyase and its application. This invention belongs to the fields of bioengineering, genetic engineering, and enzyme engineering, and relates to a C-terminal truncated alginate lyase TY2 designed with molecular docking assistance, its encoding gene, recombinant vector, strain, and its application in the preparation of low-polymerization degree alginate oligosaccharides. Using wild-type MhAly6 as the parent, the truncation boundary was determined through structural prediction and molecular docking. A portion of the linker peptide was retained, and the C-terminal GH28 family domain was deleted to obtain the truncated form TY2. TY2 has approximately twice the specific activity of the wild-type enzyme, and even higher residual activity after incubation at 45°C for 1 hour, achieving a synergistic improvement in catalytic activity and thermal stability. + The relative enzyme activity reached 4.3 times that of the control group, which can degrade pretreated Sargassum powder. The product is mainly ΔDP2–ΔDP4 low-polymerization brown algae oligosaccharides, which are suitable for related enzymatic degradation and oligosaccharide preparation.