34results about How to "Avoid off-target effects" patented technology

The invention discloses a tripterine-dendritic macromolecular conjugate, a preparation method thereof and an application, and relates to a tripterine. The tripterine-dendritic macromolecular conjugatecomprises a center dendritic polyamide-organic polyamidoaminedendrimer nano-carrier, polyethylene glycol, surface targeting ligands and the tripterine. The preparation method of the conjugate includes the steps: performing partial carboxylation on amidogen on the surface of PAMAM (polyamidoaminedendrimers) by butanedioic anhydride; dialyzing and freeze-drying a partial carboxylation object to obtain a PAMAM-COOH derivative; activating the PAMAM-COOH derivative by EDC / NHS, and modifying the activated derivative by the polyethylene glycol; dialyzing the modified derivative to obtain the PAMAM-PEG-COOH derivative; activating the PAMAM-PEG-COOH derivative by EDC / NHS; connecting the activated PAMAM-PEG-COOH derivative with EpCAM targeting aptamers; removing unreacted aptamers in an ultra-filtering manner to obtain a multifunctional PAMAM derivative; dissolving the tripterine by solvents; activating the dissolved tripterine by EDC / NHS; covalently complexing the activated tripterine on the surface of the PAMAM derivative; dialyzing a complexed object to obtain the conjugate.

The present invention relates to a nucleic acid inducing RNA interference modified for preventing off-target, and a use thereof, and more specifically, to a nucleic acid inducing RNA interference, modified by replacing, by a spacer capable of no base pairing, 5' terminal and 3' terminal regions in at least one single strand of the double strand of the nucleic acid inducing RNA interference. The nucleic acid inducing RNA interference of the present invention can provide: a nucleic acid having a novel modified form for preventing an off-target effect generated when inhibiting the expression of a target gene by an RNA interference phenomenon; and a method for selectively inhibiting the expression of a target gene by using the same. In addition, the nucleic acid inducing RNA interference according to the present invention solves the inaccuracy and side effects due to off-target, which are the problems of a known nucleic acid inducing RNA interference, by providing a nucleic acid inducing RNA interference as a novel modified form having target selectivity and specificity by preventing an off-target effect while inhibiting the expression of a target gene, and thus can be used, without worries, in the research of a technique for inhibiting the expression of a gene and in gene therapy.

The present invention provides short activating RNA molecules which up-regulate albumin production. The present invention also provides methods of up-regulating albumin production, such methods involving the use of short activating RNA molecules capable of increasing the expression of albumin. The present invention also provides the use of the short activating RNA molecules in therapy, such as treating or preventing a hyperproliferative disorder and / or a disorder characterised by hypoalbuminemia.

The present invention provides an anti-ErbB2 single chain antibody, a human ErbB2-targeting chimeric antigen receptor, a recombinant vector, a recombinant cell, and an application thereof, and pertains to the technical field of immunobiotherapy for tumors, where the anti-ErbB2 single chain antibody has an amino acid sequence depicted in SEQ ID No.1; the human ErbB2-targeting chimeric antigen receptor has an amino acid sequence depicted in SEQ ID No.3; the recombinant vector includes a gene encoding the chimeric antigen receptor and an initial vector; the recombinant cell includes a natural killer (NK) cell and the recombinant vector. The anti-ErbB2 single-chain antibody of the present invention is capable of recognizing tumor cell specifically, thereby, avoiding the off-target effects of the CAR-NK cells, and having excellent cytotoxixitc effects to tumor cell continuously; the recombinant cell is capable of having a higher cytotoxixity to tumor cell and reducing the risk of cytokine storm.

The present invention provides a Sorafenib-gene-co-loaded nano-medicine for cancer treatment and its preparation method and application, wherein Sorafenib-gene-co-loaded nano-medicine includes nano-aggregates wrapped by targeting lipid layer ; The targeting lipid layer includes Sorafenib, phospholipids, targeting substances and cholesterol; the nano-aggregates are shUSP22 encapsulated by active oxygen responsive materials. The above preparation method includes the following steps: wrapping shUSP22 with active oxygen corresponding materials to prepare nano-aggregates; loading the targeting lipid layer on the surface of nano-aggregates to obtain sorafenib-gene co-carrying nano-medicines. The above application is the application in the preparation of medicines for treating cancer. The sorafenib-gene co-loaded nano-medicine of the present invention can effectively increase the level of active oxygen in cancer cells, inhibit the expression of USP22 in liver cancer cells, efficiently kill liver cancer cells, prolong the blood circulation time of sorafenib, and inhibit tumor growth.

The invention provides a chimeric antigen receptor immune cell and a preparation method and application thereof. The expressed CAR molecule includes a signal peptide, a binding receptor of the coronavirus spike glycoprotein, a hinge region, a transmembrane domain, and a costimulatory structure. domain and signaling domain; the CAR molecule also includes secretory ACE2, which is connected to the carboxyl terminus of the signaling domain through a linking peptide; the immune cells expressing the CAR molecule have the ability to target and clear the cells infected by the new coronavirus, and Release secreted ACE2 molecules to competitively bind to the viral S protein to achieve allogeneic reinfusion to treat people infected with COVID-19 and prevent the transformation from mild to critically ill. It also has universal curative effect on other viruses bound by ACE2 receptors, and has strategic reserve value It provides new methods and ideas for the treatment of many major human diseases such as tumors and immune diseases.

The invention discloses a nucleic acid molecule encoding a chimeric antigen receptor, the chimeric antigen receptor comprises an extracellular region, a transmembrane region and an intracellular signal transduction region, and the encoded extracellular region comprises a FLT3 binding A structural domain, the FLT3 binding domain is a FLT3 ligand or an amino acid sequence having 90-99% identity with the FLT3 ligand. Through flow cytometry, degranulation analysis experiments, and ELISA detection of cytokines secreted by T cells, it was proved that the T cells modified by the chimeric antigen receptor had a strong killing effect on leukemia cells expressing FLT3, especially for those carrying FLT3 mutant AML cells have a specific killing effect, effectively preventing off-target effects. The chimeric antigen receptor FLT3L-CD8α-4-1BB-CD3ζ of the present invention can be used for FLT3 + Treatment of leukemia, especially leukemia with FLT3 mutation.

The invention discloses a nucleic acid molecule encoding a chimeric antigen receptor targeting CD123, the chimeric antigen receptor comprises an extracellular region, a transmembrane region and an intracellular signal transduction region, and the encoded extracellular region comprises CD123 binding domain, the CD123 binding domain is an anti-CD123 single-chain antibody variable region fragment; the anti-CD123 single-chain antibody variable region fragment is the amino acid sequence shown in SEQ ID NO.13 or has 90 A sequence with %-99% identity, the amino acid sequence shown in SEQ ID NO.14 or a sequence with 90%-99% identity therewith, or the amino acid sequence shown in SEQ ID NO. % identity sequence. The chimeric antigen receptor of the present invention can be used for CD123 + and / or CD33 + The treatment of hematological tumors can effectively prevent off-target effects, make the treatment effect better, and avoid escape.