237 results about "Targeted Modification" patented technology

Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and / or the rat Rag2 / Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR / Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.

Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and / or the rat Rag2 / Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR / Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.

Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR / Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.

The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate the unnatural amino acid phenylselenocysteine into proteins produced in eubacterial host cells such as E. coli. The invention provides, for example but not limited to, novel orthogonal aminoacyl-tRNA synthetases, polynucleotides encoding the novel synthetase molecules, methods for identifying and making the novel synthetases, methods for producing proteins containing the unnatural amino acid phenylselenocysteine and translation systems. The invention further provides methods for producing modified proteins (e.g., lipidated proteins) through targeted modification of the phenylselenocysteine residue in a protein.

Compositions for targeted mutagenesis of cell surface receptors for HIV and methods of their use are provided herein. The compositions include triplex-forming molecules that displace the polypyrimidine strand of target duplex and form a triple-stranded structure and hybrid duplex in a sequence specific manner with the polypurine strand of the target duplex. The triplex-forming molecules include a mixed-sequence “tail” which increases the stringency of binding to the target duplex, improves the frequency of modification at the target site, and reduces the requirement for a polypurine:polypyrimidine stretch. Methods for using the triplex-forming molecules in combination with one or more donor oligonucleotides for targeted modification of sites within or adjacent to genes that encodes cell surface receptors for human immunodeficiency virus (HIV) are also disclosed. Methods for ex vivo and in vivo prophylaxis and therapy of HIV infection using the disclosed compositions are also provided.

Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR / Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.

Methods of making a targeted modification in a male fertility gene in the genome of a plant are disclosed. The methods involve contacting a plant cell with an engineered double-strand-break-inducing agent capable of inducing a double-strand break in a target sequence in the male fertility gene and identifying a cell comprising an alteration in the target sequence. Also disclosed are plants, plant cells, plant parts, and seeds comprising a male fertility gene with an alteration in a male fertility gene. Nucleic acid molecules comprising male fertility genes with at least one targeted modification therein, optimized nucleic acid molecules encoding endonucleases that are engineered double-strand-break-inducing agents and expression cassettes, host cells, and plants comprising one or more of the nucleic acid molecules are further disclosed.

The invention discloses a method for acquiring gene editing sheep by RNA-mediated specific double-gene knockout and special sgRNA for the method. The sgRNA combination consists of sgRNAMSTN-1 and sgRNAFGF5-1, wherein sgRNAMSTN-1 is sgRNA which can realize specific targeted modification of sheep MSTN gene and is RNA shown in the second to 21st nucleotides in a sequence 6 or RNA with the second to 21st nucleotides of the sequence 6; sgRNAFGF5-1 is sgRNA which can realize specific targeted modification of sheep FGF5 gene and is RNA shown in the second to the 21st nucleotides in a sequence 8 or RNA with the second to 21st nucleotides of the sequence 8. According to the method for acquiring gene editing sheep by RNA-mediated specific double-gene knockout and special sgRNA for the method, the CRISPR / Cas9 genome editing technology and the micro-injection technology are combined, so that the sheep targeting efficiency is higher and more accurate, sheep double-gene knockout is realized for the first time in the generation, improvement on sheep meat production and wool production is greatly promoted, and a larger space and a more effective technical tool are provided for breeding of new sheep varieties.

A variety of methods and compostions are provided, including methods and compositions for targeted modification of a specific target site in a cell or organism, methods for integrating polynucleotides of interest, methods to assess promoter activity, directly select transformed organisms, minimize or eliminate expression resulting from random integration into the genome of an organism, such as a plant, remove polynucleotides of interest, combine multiple transfer cassettes, invert or excise a polynucleotide, silence a gene, and identify and / or characterize transcriptional regulating regions. The methods involve the introduction of a cell proliferation factor and a double-strand break-inducing enzyme into an organism.

Devices, systems, and methods for detecting protein-nucleic acid and cell-nucleic acid hybridization, using surface-tethered aptamer probes, without the use of labeling or target modification and capable of recycling.

Devices, systems, and methods for detecting nucleic acid hybridization, including single nucleic base mutations at low concentrations, are disclosed, using capture units having nanoparticles with attached single-stranded oligonucleotides that are capable of hybridizing target oligonucleotides and reporter molecules having nanoparticles with attached single-stranded oligonucleotides, without the use of labeling or target modification.

The invention discloses a molecular genetic improvement method for lowering rice seed holding by targeted modification on rice seed holding gene qSH1 by using a CRISPR (clustered regularly interspaced short palindromic repeats) / Cas9 system. The method comprises the following steps: 1) selecting an appropriate target; 2) establishing a vector containing the target spot sequence; 3) establishing a recombinant vector containing the target spot sequence by utilizing the vector; 4) introducing the recombinant vector into receptor rice to obtain a transgenic positive plant; 5) obtaining a targeted-mutation mutant plant by utilizing the transgenic positive plant; 6) carrying out additive-generation growth on the mutant plant to obtain a transgenic-component-free homozygous mutant plant; and 7) carrying out seed holding investigation by using the homozygous mutant plant to obtain the plant with obviously lower seed holding as the seed-holding-improved plant. The method has the advantages of high directionality, small genetic background changes and the like, can avoid the risks caused by genetic transformation, and can culture the new species and new combination of transgenic-component-free rice with obviously lower seed holding.

Therapeutic drug delivery and diagnostics systems comprise biologically active compounds associated with particulate carriers of less than 20 nm. These systems can be utilised for targeted modification of growth, development and functions, such as gene expression, protein synthesis, intracellular energy production and transport mechanisms in prokaryotic and eukaryotic organisms. The systems are also applicable for controlled modification of structural and functional properties of extracellular components and tissue constituents. The characteristics of a biological site are evaluated and an entity is provided which is dependent on the site characteristics. The entity comprises nanoparticles of less than 20 nm. A probe comprising nanoparticles of less than 5 nm is also provided.

The invention discloses a method for obtaining sheep with different hair colors on the basis of CRISPR / Cas9 and sgRNA of a targeted ASIP gene. The invention provides sgRNA (ASIP-sgRNA) capable of achieving specific and targeted modification of a sheep ASIP gene, and the sgRNA (ASIP-sgRNA) is RNA as shown from the third nucleotide to the 22<nd> nucleotide of 5' tail end of a sequence 4 of a sequence list or RNA with the nucleotides from the third nucleotide to the 22<nd> nucleotide of the 5' tail end of the sequence 4 of the sequence list. The ASIP-sgRNA particularly can be the RNA as shown in the sequence 4 of the sequence list. The invention further provides a method for obtaining sheep with changed hair colors. The method comprises the following steps that co-transfection of sgRNA capable of achieving specific and targeted modification of the sheep ASIP gene and Cas9mRNA on sheep cells is conducted, and therefore the sheep ASIP gene is deleted, and the sheep with the changed hair colors are obtained. According to the method for obtaining the sheep with different hair colors on the basis of CRISPR / Cas9 and sgRNA of the targeted ASIP gene, a CRISPR / Cas9 genome-editing technology is combined with a microinjection technology, and an effective technological means is provided for artificially changing the hair colors of the sheep.

An improved nanoparticle for transfecting cells is provided. The nanoparticle includes a core polyplex and a silica coating on the core polyplex and, optionally, a polymer attached to an outer surface of the silica coating , where the polyplex includes an anionic polymer, a cationic polymer, a cationic polypeptide, and a polynucleotide. Also provided is an improved method of modifying intracellular polynucleotides. The method includes contacting a cell with a nanoparticle that includes a core polyplex and a silica coating on the core polyplex and, optionally, a polymer attached to an outer surface of the silica coating, where the polyplex includes an anionic polymer, a cationic polymer, a cationic polypeptide, and a polynucleotide.

The invention discloses a targeted polypeptide capable of being specifically combined with tumors, particularly a targeted peptide capable of being specifically combined with liver cancer tissues and application thereof in diagnosis and treatment of liver cancer. The liver cancer targeted peptide is preferably HCC-47 of which the amino acid sequence is SQDIRTWNGTRS; and the liver cancer targeted peptide is specifically combined with the liver cancer tissues, and can not be specifically combined with cervical carcinoma cells Hela, mammary cancer cells MDA-MB231, kidney cancer cells CRL-1932 and lung cancer cells A549. The polypeptide is obtained by in-vitro biological elutriation by combining a bacteriophage display library and a living body cross sectioning technique. The polypeptide can be used in a molecular imaging preparation for early diagnosis of liver cancer. The polypeptide can also be used in targeted modification and preparation of drugs for treating liver cancer. The polypeptide can also be used for targeted modification on drug transport carriers, thereby providing a new way for diagnosing or treating patients with liver cancer.

The invention discloses a pair of transcription activator-like effector nucleases, and encoding genes and application thereof. The pair of transcription activator-like effector nucleases (TALEN) is obtained by fusing a pair of deoxyribonucleic acid (DNA) recognition proteins and two heterologous subunits of a Flavobacterium okeanokoites 1(Fok 1) DNA incision enzyme and can recognize two adjacent loci on goat or sheep beta lactoglobulin gene (BLG) exon2 specifically. When the transcription activator-like effector nucleases are transferred to a host cell simultaneously, the exon2 loci of the BLG gene of the host cell can be targeted by the transcription activator-like effector nucleases, and the targeted loci are subjected to genetic mutation, so that the targeted modification of the goat or sheet BLG gene is realized, and the transcription activator-like effector nucleases have the advantages of high specificity, high targeting efficiency, high accuracy and the like.

Devices, systems, and methods for detecting protein-nucleic acid and cell-nucleic acid hybridization, using surface-tethered aptamer probes, without the use of labeling or target modification and capable of recycling.

Devices, systems, and methods for detecting nucleic acid hybridization, including single nucleic base mutations at low concentrations, are disclosed, using surface-tethered hairpin loop oligonucleotide probes and metal-nanoparticles conjugated to a hybridization detection sequence that is capable of binding the stem region of the opened hairpin loop oligonucleotide probe, without the use of labeling or target modification and capable of recycling.

The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate the unnatural amino acid phenylselenocysteine into proteins produced in eubacterial host cells such as E. coli. The invention provides, for example but not limited to, novel orthogonal aminoacyl-tRNA synthetases, polynucleotides encoding the novel synthetase molecules, methods for identifying and making the novel synthetases, methods for producing proteins containing the unnatural amino acid phenylselenocysteine and translation systems. The invention further provides methods for producing modified proteins (e.g., lipidated proteins) through targeted modification of the phenylselenocysteine residue in a protein.

The embodiment of the invention discloses a data modification and synchronization method, apparatus and device and a storage medium of a block chain. The data modification method of the block chain isapplied to inspect the inspection node in the block chain network. The method comprises the following steps: the inspection node obtains at least one synchronization block from an ordinary node, andthe synchronization block is an ordinary block; The checking node checks the data of the synchronous block according to the set modification rules to determine the target modification data; The inspection node modifies the target modification data; The checking node generates a checkpoint according to the synchronization block, and calculates and generates a checkpoint mark according to the data of the synchronization block. The checking node associates the checkpoint identifier with the synchronization block for recording; The checking node confirms the checkpoint identification by the checking node in the checking block chain network for storing in the checking block. A synchronization block is used for synchronous downloading of a common node. Through the technical proposal provided bythe embodiment of the invention, harmful data can be removed from the block chain.

Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and / or the rat Rag2 / Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

The embodiment of the invention discloses a data modification method, apparatus,equipment and a medium of a block chain. The method comprises the following steps: obtaining a block data modification message; determining a target modification block to be modified according to the block data modification message; modifying block data in a target modification block according to the block data modification message; taking a previous block of the target modification block as a redo start block, reprocessing transaction data in the target modification block and subsequent blocks to generate a new block chain, and connecting the new block chain to the redo start block; subsequent blocks subsequent to the redo start block are discarded. The technical proposal of the embodiment of the invention canrealize the modification of the block chain data, and provides an effective solution for the modification of the block chain data.

The invention relates to a dasatinib liposome preparation, and a preparation method thereof. The dasatinib liposome preparation is high in biocompatibility; target modification can be carried out; sustained and controlled release of dasatinib can be realized; and it is beneficial for maintenance of relatively high plasma drug concentration in a long term, improvement of drug distribution, and increasing of drug bioavailability. The dasatinib liposome preparation possesses excellent lipophilic performance, is capable of passing through phospholipid bilayer in a molecular form and entering into inner water phase; pH value of liposome inner water phase is relatively low, the dasatinib moleculars are capable of bonding with hydrogen ions so as to form dasatinib ions, and combination with anions in an ammonium salt solution and forming of insoluble salts are realized, diffusion of dasatinib in the inner water phase into an outer water phase is inhibited, dasatinib is coated by the liposome inner water phase steadily, encapsulation efficiency and storage stability are improved, and excellent in-vitro slow release effect is achieved.

The embodiment of the invention discloses a data modification and block verification method and device, an apparatus and a medium of a block chain. The method comprises the following steps: obtaininga block data modification message; Determining a target modification block to be modified according to the block data modification message; Modifying block data in a target modification block according to the block data modification message; Determining a synchronization group and a synchronization signature of the target modification block according to the modified target modification block, wherein the synchronization signature of the synchronization group is used in place of the verification function of the block identification, and when the synchronization signature is verified to be passed, it is determined that the target modification block is verified to be passed. Through the technical scheme of the embodiment of the invention, the modification of the block chain data can be realized, the problem that the prior block chain technology is difficult to modify the transaction data is solved, and a simple and effective solution is provided for modifying the block chain data.

The invention discloses a database modification SQL (Structured Query Language) generation method and system, a storage medium, and a computer device. The method includes: analyzing a source databaseand a target database so as to acquire a source table data structure corresponding to the source database and a target table data structure corresponding to the target database respectively, wherein the source table data structure and the target table data structure include field data and index data; performing comparison analysis on the field data and the index data in the same class in the source table data structure and the target table data structure respectively so as to generate corresponding differential SQLs; and summarizing all the differential SQLs so as to generating a target modification SQL. The invention can solve the problem of complex operations and low efficiency in the prior art.

The invention discloses a method and a system for carrying out functional solidification and providing services by adopting a binary system. According to the method and the system, by virtue of targeted modification through a cross-platform general communication transmission method, the whole system is endowed with extremely high performance, and meanwhile, a high-performance API (Application Programming Interface) communication interface packaging method is realized between a binary program and a binary program as well as a binary program and an external program, so that the requirements on the service stability and the technical extensibility are met; the burden of developers is greatly alleviated, the software development efficiency is improved, the whole system has extremely high performance, the experience of the system is improved, and the requirements on the flexibility and the performance index of a software system in the age of intelligence can be better met.