10results about How to "Reduce off-target effects" patented technology

The present application relates to an ATP-responsive lipid, a nucleic acid nano-preparation and a preparation method. The structural formula of the ATP-responsive lipid is shown in the following formula (I). The ATP-responsive lipid and the nucleic acid nano-preparation of the present application can be combined with ATP under the condition of high ATP level in cells, increase the fluidity of the membrane, promote the fusion of the lipid nanoparticle and the endosome membrane, destroy the integrity of the endosome membrane, increase the efficiency of lysosome escape, and then improve the efficiency of nucleic acid delivery and expression.

This invention provides the application of a siRNA composition targeting LOC157273 in the preparation of drugs for treating non-alcoholic steatohepatitis (NASH) and liver fibrosis, belonging to the field of biomedical technology. The siRNA of this invention directly corrects the hyperlipidemic hepatic lipid synthesis, insulin resistance, and inflammatory activation caused by abnormal expression of PPP1R3B by specifically silencing the key fibrosis driver gene LOC157273. This fundamentally blocks the activation of hepatic stellate cells and excessive extracellular matrix deposition, achieving precise reversal of the fibrosis process and blocking the occurrence of NASH. The siRNA delivery system is optimized through liver-targeted modification, improving liver enrichment efficiency and reducing off-target effects caused by systemic distribution. It exhibits strong targeting, directly acting on upstream regulatory genes of fibrosis and NASH. Simultaneously, it silences multiple synergistic pathogenic gene sites, enhancing therapeutic efficacy and providing a highly efficient and safe novel intervention for liver fibrosis and NASH.

This invention discloses a transgenic recombinant immune cell that specifically targets tumors. The recombinant immune cell comprises a chimeric polypeptide and a chimeric antigen receptor; the chimeric polypeptide includes a first extracellular region, a first transmembrane region, and a first intracellular region with HLA-G protein binding activity, wherein the N-terminus of the first transmembrane region is connected to the C-terminus of the first extracellular region, and the N-terminus of the first intracellular region is connected to the C-terminus of the first transmembrane region; the first transmembrane region includes the transmembrane region of the Notch receptor protein from Xenopus laevis; the antigen-chimeric receptor does not have HLA-G protein binding activity. This recombinant immune cell significantly improves the precise recognition of tumor cells by immune cells, reduces off-target effects of cell therapy, and accurately and effectively distinguishes tumor cells from normal cells, providing an effective target and targeting method for the treatment of broad-spectrum tumors (especially solid tumors).

The invention provides application of ANKRD13A in preparation of drugs and diagnostic reagents for intestinal cancer, relates to the technical field of biomedicine, and is technically characterized by providing application of ANKRD13A as a therapeutic target in preparation of drugs for preventing and / or treating intestinal cancer. Close association between ANKRD13A and occurrence and development of the intestinal cancer is defined through a series of verification experiments. Clinical sample analysis shows that transcript abundance and protein expression level of ANKRD13A in a colon cancer tissue are remarkably lower than those in a normal colon tissue; the cell level verification proves that the mRNA and protein expression of ANKRD13A in the colon cancer cell line is obviously reduced compared with that of a normal colon epithelial cell line; animal experiments show that an Ankrd13a gene-deficient mouse is induced by AOM / DSS, the occurrence rate of colorectal tumors is higher, the number of the tumors is larger, and tumor tissues have medium-high-grade canceration characteristics along with abnormal expression of beta-Catenin, nuclear ectopic, increase of Ki67 positive cells and other malignant pathological expressions. The experimental results jointly prove that expression deletion or down-regulation of ANKRD13A is closely related to occurrence risk increase of intestinal cancer.

The present invention is directed to provide novel RNA molecules. The RNA molecules are for RNA interference to target a mutant allele with a point mutation, in which (1) the molecule has a nucleotide sequence complementary to a nucleotide sequence of a coding region of the mutant allele; and (2) when counted from the base at the 5'-end in the nucleotide sequence complementary to the nucleotide sequence of the mutant allele, (2-1) a base at position 5 or 6 is mismatched with a base in the mutant allele; (2-2) a base at position 10 or 11 is at the position of the point mutation and is identical to the base at the position of the point mutation in the mutant allele; (2-3) the group at the 2'-position of the pentose in the ribonucleotide at position 8 is modified with OCH3, halogen, or LNA; and (2-4) the group at the 2'-position of the pentose in the ribonucleotide at position 7 is not modified with any of OCH3, halogen, and LNA. In this RNA molecule, one or more ribonucleotides may be each replaced by, e.g., a deoxyribonucleotide. The molecule may form a double-stranded RNA with a complementary strand.

This invention discloses a transgenic recombinant immune cell that specifically targets tumors. The recombinant immune cell comprises a chimeric polypeptide and a chimeric antigen receptor; the chimeric polypeptide includes a first extracellular region, a first transmembrane region, and a first intracellular region with HLA-G protein binding activity, wherein the N-terminus of the first transmembrane region is connected to the C-terminus of the first extracellular region, and the N-terminus of the first intracellular region is connected to the C-terminus of the first transmembrane region; the first transmembrane region includes the transmembrane region of the Notch receptor protein from Xenopus laevis; the antigen-chimeric receptor does not have HLA-G protein binding activity. This recombinant immune cell significantly improves the precise recognition of tumor cells by immune cells, reduces off-target effects of cell therapy, and accurately and effectively distinguishes tumor cells from normal cells, providing an effective target and targeting method for the treatment of broad-spectrum tumors (especially solid tumors).

The present application relates to the technical field of nanobody, in particular to anti-CLDN6 nanobody and its application. The present application provides a kind of anti-CLDN6 nanobody with high affinity and specificity. The nanobody can specifically recognize and bind to the CLDN6 target of various solid tumors, including ovarian cancer, liver cancer, endometrial cancer, testicular cancer and gastric cancer, etc. The nanobody of the present application can be used as a core recognition element to construct a variety of therapeutic and diagnostic platforms such as chimeric antigen receptor T cells, NK cells, bispecific antibodies, antibody drug conjugates or molecular imaging probes. The technical solution can solve the technical problem of lack of high specificity anti-CLDN6 nanobody in the prior art, and provide an effective means for the immunotherapy of CLDN6 positive solid tumors.

This invention relates to the field of nanobody technology, specifically to anti-CLDN6 nanobodies and their applications. This invention provides a class of anti-CLDN6 nanobodies with high affinity and specificity. These nanobodies can specifically recognize and bind to CLDN6 targets in various solid tumors, including ovarian cancer, liver cancer, endometrial cancer, testicular cancer, and gastric cancer. The nanobodies of this invention can serve as core recognition elements for constructing various therapeutic and diagnostic platforms, such as chimeric antigen receptor T cells, NK cells, bispecific antibodies, antibody-drug conjugates, or molecular imaging probes. This technical solution addresses the technical problem of the lack of highly specific anti-CLDN6 nanobodies in existing technologies, providing an effective means for the immunotherapy of CLDN6-positive solid tumors.

The present invention is directed to provide novel RNA molecules. The RNA molecules are for RNA interference to target a mutant allele with a point mutation, in which (1) the molecule has a nucleotide sequence complementary to a nucleotide sequence of a coding region of the mutant allele; and (2) when counted from the base at the 5'-end in the nucleotide sequence complementary to the nucleotide sequence of the mutant allele, (2-1) a base at position 5 or 6 is mismatched with a base in the mutant allele; (2-2) a position 10 or 11 corresponds to the position of the point mutation; and (2-3) the group at the 2'-position of the pentose at positions 6-8 or positions 7 and 8 is modified with, e.g., OCH3. In this RNA molecule, one or more ribonucleotides may be each replaced by, e.g., a deoxyribonucleotide. The molecule may form a double-stranded RNA with a complementary strand.

The invention belongs to the technical field of biological vaccine preparation, and particularly relates to a preparation method of a targeted antigen displayed MS2 phage VLPs nanoparticle vaccine. The preparation method sequentially comprises the following steps: preparation and activation of a targeting ligand, fixed-point transformation and expression of MS2 bacteriophage capsid protein, preparation of targeting antigen-aptamer fusion protein, folding optimization and activity pre-verification of the antigen-aptamer fusion protein, self-assembly and antigen display of targeting MS2-VLPs, purification and characterization of targeting VLPs nanoparticles, and preparation of the vaccine preparation. On the basis, by introducing the targeting ligand aiming at the specific receptor on the surface of the antigen presenting cell, accurate recognition and combination of the VLPs vaccine on the target cell are realized, the problem that the antigen display lacks targeting is fundamentally solved, the antigen delivery efficiency is remarkably improved, the off-target effect is effectively reduced, and the antigen waste is avoided.