26 results about "Spliceosome" patented technology

The invention belongs to the field of medicinal chemistry, and particularly relates to a compound shown in a formula (I), pharmaceutically acceptable salt, deuterated substance, stereoisomer, tautomer or a mixture thereof, which can be used as a protein degradation agent for degrading an androgen receptor or a spliceosome thereof. The compound can be used for preparing medicines for treating and / or preventing diseases related to androgen receptors or spliceosomes thereof. # imgabs0 #

Disclosed are methods and compositions for promoting trans-splicing. In some embodiments, the composition comprises an engineered small nuclear RNA that promotes trans-splicing of a target RNA molecule. The composition may further comprise an RNA donor molecule.

Disclosed herein include methods, compositions, and kits suitable for use in treating a hematological cancer in a subject. In some embodiments, the method comprises determining the presence or absence of at least one mutation in one or more genes encoding a spliceosome protein in sample nucleic acids from the subject; and administering onvansertib and decitabine to the subject, if the at least one mutation in one or more genes encoding a spliceosome protein is determined to be present in the sample nucleic acids, thereby reducing or inhibiting progression of the hematological cancer in the subject.

The invention discloses a Jiangxi No. 1 CcMYB18 gene as well as a variable spliceosome and application thereof, and belongs to the technical field of plant molecular biology. The invention provides a Jiangxi No. 1 CcMYB18 gene, the nucleotide sequence of the Jiangxi No. 1 CcMYB18 gene is shown as SEQ ID NO.1 in a sequence table, and the amino acid sequence of the Jiangxi No. 1 CcMYB18 gene is shown as SEQ ID NO.3 in the sequence table. The nucleotide sequence of the variable spliceosome is as shown in SEQ ID NO.1 in a sequence table, and the amino acid sequence of the variable spliceosome is as shown in SEQ ID NO.3 in the sequence table. The CcMYB18 gene and a variable spliceosome transgenic positive strain thereof are obtained through an arabidopsis thaliana flower immersion method. Compared with WT, the whole CcMYB18 transgenic plant shows the expression that rosette leaves and stalks are obviously purple, it is determined that CcMYB18 can promote accumulation of anthocyanin, and a variable spliceosome of CcMYB18 is opposite, and an effective molecular tool is provided for improving the ornamental value of plants through genetic engineering.

A synthetic nucleic acid expression system for production of a transcript of interest in a predefined cell-state is provided, the system comprising (a) a first nucleic acid sequence comprising a first promoter operably linked to a nucleic acid sequence encoding a first trans-spliceable pre-mRNA sequence comprising at least one exon encoding a 5′ fragment of said transcript of interest and a first RNA sequence required for spliceosome-dependent trans-splicing; and (b) a second nucleic acid sequence comprising a second promoter operably linked to a nucleic acid sequence encoding a second trans-spliceable pre-mRNA sequence comprising at least one exon encoding a 3′ fragment of said transcript of interest and a second RNA sequence required for spliceosome-dependent trans-splicing; wherein said first promoter and said second promoter are different and each one is specifically regulated by said predefined cell-state.

Disclosed are methods and compositions for promoting trans-splicing. In some embodiments, the composition comprises an engineered small nuclear RNA that promotes trans-splicing of a target RNA molecule. The composition may further comprise an RNA donor molecule.

The present invention provides tumor-specific neoantigenic peptides resulting from mutations in spliceosome factor 3b subunit 1 (SF3B1), vaccinal compositions comprising such tumor-specific neoantigenic peptides, nucleic acids, antibodies or fragments thereof and immune cells that can be used in cancer therapy or prevention.

To provide compounds and pharmaceutical compositions for treating cancer.SOLUTION: The present invention provides a compound selected from the compound represented by formula (III) and a pharmaceutically acceptable salt thereof. The compound is useful for treating cancer, particularly cancers in which agents targeting the spliceosome and mutations therein are known to be useful.SELECTED DRAWING: None

The present technology relates to methods for predicting the risk of acute myeloid leukemia (AML) in a subject prior to the onset of AML symptoms, and whether such a subject will benefit from treatment with an AML therapy. The methods disclosed herein are based on detecting the presence of mutations in the nucleic acid sequences of IDH1 / 2, TP53, DNMT3A, TET2, and spliceosome genes. Kits for use in practicing the methods are also provided.

The present application relates to a primer combination for lung cancer detection and its application in lung cancer diagnosis, in particular, a technology for specifically detecting CIZ1b splice body RNA through real-time fluorescent quantitative PCR technology. The method combines blocker sequence to inhibit non-specific amplification of CIZ1a splice body by designing specific primers and probes, and ensures high-specificity detection of CIZ1b splice body RNA. The detection samples include lung cancer tissues and plasma, and cDNA is generated through reverse transcription after RNA extraction of the samples, and real-time fluorescent quantitative analysis is performed. Meanwhile, the method introduces an internal reference gene B2M for standardization correction, and improves the sensitivity and accuracy of the detection. The present application provides a non-invasive and reliable early lung cancer diagnosis tool, which has good clinical application potential.

The present invention provides tumor-specific neoantigenic peptides resulting from mutations in spliceosome factor 3b subunit 1 (SF3B1), vaccinal compositions comprising such tumor-specific neoantigenic peptides, nucleic acids, antibodies or fragments thereof and immune cells that can be used in cancer therapy or prevention.

The present disclosure provides methods of circular RNA isolation and purification. The method for preparing the target circular RNA in vitro through intron self-splicing comprises the following steps: (a) providing a circular RNA in vitro transcription template; (b) carrying out in-vitro transcription by using the template to form an in-vitro transcription product; (c) carrying out self-splicing cyclization on the in-vitro transcription product to form an in-vitro cyclization product; in any one or more of steps (a)-(c), the cleaved introns and / or uncyclized linear RNA precursors in the in vitro cyclization product can be acidified by the polyX glycoside so as to carry a polyX glycoside acid (polyX, X = A, U, C or G) tag; and (d) enabling the in-vitro cyclization product to be in contact with the polyX glycoside acid specific binding substance, and removing the cut intron with the polyX tag and the non-cyclized linear RNA precursor with the polyX tag in the product to obtain the target circular RNA. The invention further provides a corresponding product and application.

The present disclosure provides engineered polynucleotides that interact with mRNA precursors and spliceosomes to modulate gene expression. The engineered polynucleotides may have a stem-loop structure having a recruitment spliceosome and a targeting sequence complementary to the target sequence at the exon-intron splice point, and may include nucleotides having a 2'modification and a thiophosphate linkage The engineered polynucleotides may be administered to a subject to treat a neurodegenerative disease.

The present invention discloses the application of bovine SP110 gene splicing editing in enhancing the anti-tuberculosis ability of cattle, belonging to the technical field of bovine anti-tuberculosis breeding. The present invention starts from splicing-related cis-acting elements, and regulates the alternative splicing reaction of bovine SP110 by introducing cis-acting elements, thereby affecting the anti-tuberculosis ability of cattle. The cis-acting element sequence is named the pre-SAND-exon sequence, which is located in exon 12 and the adjacent 5'-terminal intron 12 of the human or equine SP110 gene, and the sequences are shown in SEQ ID NO.1 and SEQ ID NO.2. The present invention first regulates the alternative splicing of the bovine SP110 gene by introducing the pre-SAND-exon sequence into the bovine SP110 gene, reduces the expression abundance of the spliceosome bSP110c with lower anti-tuberculosis ability, and regulates the higher abundances of the spliceosomes bSP110a and bSP110b with anti-tuberculosis infection ability. The provided bovine SP110 gene splicing editing can effectively improve the anti-tuberculosis ability of cattle, can be used for the breeding of anti-tuberculosis cattle, effectively simplifies the breeding method, improves the breeding efficiency, and saves the breeding cost.

The invention discloses an expression method of amylase in pichia pastoris, and belongs to the field of gene engineering. The method is characterized in that pGAPZ alpha A is used as a carrier, a translation-related functional gene is inserted between a GAP promoter and an AOX1 terminator to construct a recombinant plasmid, and the translation-related functional gene is selected from a coding protein kinase gene, a coding cytoplasm RNA binding protein gene or a coding spliceosome protein gene; and after linearization, electrotransduction is carried out to introduce into pichia pastoris containing barley alpha-amylase genes, and fermentation is induced through screening. According to the method, related functional genes are translated through co-expression, the secretory expression of amylase is remarkably improved, the enzyme activity is improved by 106.9% at most, and industrial production requirements are met.

The invention relates to the technical field of biomedicine, in particular to a long-fragment amplification analysis method and amplification kit for HBV RNA splices.The long-fragment amplification analysis method for the HBV RNA splices.The long-fragment amplification analysis method for the HBV RNA splices.The long-fragment amplification analysis method for the HBV RNA splices.The method comprises the following steps that viral nucleic acid is extracted, and DNA in the viral nucleic acid is removed; performing reverse transcription by using an HBV specific primer to obtain cDNA (complementary deoxyribonucleic acid); selecting an amplification primer capable of identifying a full-length region of the HBV genome from a conserved region of the HBV genome, and further performing PCR amplification; the obtained PCR amplification product is subjected to library building and single molecule sequencing, and obtained sequencing data is analyzed to obtain the type and proportion of HBV RNA spliceosomes; the invention also discloses an amplification kit, the amplification kit comprises a first chain cDNA synthesis reagent, a DNA digestion reaction solution, an HBV specific reverse transcription primer, a buffer solution, an inhibitor, a dNTP mixture, a reverse transcriptase, distilled water and a thermal stable DNA invertase, and a library building sequencing analysis process is optimized to solve the problem that the level of HBV RNA and spliceosome of an HBeAg negative patient infected by hepatitis B virus is relatively low.

The invention provides a construction method of an expression vector of eukaryotic genes in prokaryotes, and belongs to the field of molecular biology. The method comprises the following steps: (a) designing a PCR (Polymerase Chain Reaction) primer pair for amplifying each exon in a specific transcription spliceosome cds sequence; (b) respectively amplifying each exon by using the PCR primer pair designed in the step (a) to obtain a PCR fragment of each exon; (c) mixing the n exon fragments obtained in the step (b) as a template, and carrying out overlapping PCR by using the forward primer P1-F of the first exon and the reverse primer Pn-R of the final exon to obtain a complete cds fragment of the specific transcription spliceosome; and (d) purifying and recovering the cds fragment of the specific transcription spliceosome obtained in the step (c), and connecting the cds fragment to a prokaryotic expression vector. Therefore, the problem that the cds fragment of the target transcription spliceosome cannot be obtained due to unknown temporal-spatial expression information of a luxury gene or a specific transcript is solved.

The invention discloses an application of cattle SP110 gene splicing editing in enhancing the anti-tuberculosis ability of cattle, and belongs to the technical field of cattle anti-tuberculosis breeding, starting from splicing related cis-acting elements, the variable splicing reaction of the cattle SP110 is regulated by introducing the cis-acting elements, so that the anti-tuberculosis ability of the cattle is influenced. The sequence of the cis-acting element is named as a pre-SAND-exon sequence, the cis-acting element is located on the 12th exon of a human or horse SP110 gene and the 12th intron adjacent to the 5'end of the human or horse SP110 gene, and the sequences of the cis-acting element are shown as SEQ ID NO.1 and SEQ ID NO.2. According to the invention, the pre-SAND-exon sequence is introduced into the cattle SP110 gene for the first time, so that the variable splicing of the cattle SP110 gene is regulated and controlled, the expression abundance of a splicing body bSP110c with relatively low anti-tuberculosis capability is reduced, and the abundance of bSP110a and bSP110b splicing bodies with anti-tuberculosis infection capability is regulated and controlled to be higher. The provided cattle SP110 gene splicing editing can effectively improve the anti-tuberculosis ability of cattle, can be used for breeding anti-tuberculosis cattle, effectively simplifies the breeding method, improves the breeding efficiency, and saves the breeding cost.

This disclosure provides an engineered polynucleotide that interacts with a pre-mRNA and a spliceosome to regulate gene expression. The engineered polynucleotide may have stem-loop structure that recruits the spliceosome and targeting sequences that are complementary to a target sequence at an exon-intron splice junction and may include nucleotides with 2′ modifications and phosphorothioate linkages. The engineered polynucleotide can be administered to a subject to treat a cancer.

The invention belongs to the technical field of aquatic organisms, and particularly relates to dsRNA interference primers for regulating a sex gene Dmrta2 of blue crabs as well as a method and application of the dsRNA interference primers. The invention provides dsRNA (double-stranded ribonucleic acid) for regulating and controlling a sex gene of blue crab Dmrta2. The dsRNA is obtained by taking a spliceosome sequence as a template through in-vitro transcription; the invention also provides an RNA interference method for regulating and controlling testis development of scylla paramamosain by using the Dmrta2 gene variable spliceosome. The method comprises in-vivo interference treatment and in-vitro interference treatment. The result of the embodiment shows that the RNA interference is implemented in the in-vivo and in-vitro tissue culture of the scylla paramamosain by the method, the expression interference of the Dmrta2 gene variable spliceosome can be successfully completed, and the retardation or abnormality of sperm generation and the tissue change of sperm cavity after the interference of the Dmrta2 gene variable spliceosome can be successfully observed.

This invention discloses the application of the OsCAX1a gene in the breeding of cold-adapted rice varieties, belonging to the field of plant genetic engineering. The amino acid sequences of the two different spliceosome translation proteins encoded by the OsCAX1a gene are shown in SEQ ID NO.1 and SEQ ID NO.2, respectively, and the CDS sequences are shown in SEQ ID NO.3 and SEQ ID NO.4, respectively. This invention reveals that OsCAX1a is a negative regulator of rice cold stress adaptation. Knocking out the OsCAX1a gene inhibits rice growth and development in the early stages, but as the heading stage lengthens and the plant enters the low-temperature growth period, the mutant exhibits significantly better cold adaptation, ultimately manifested in an increased number of tillers and increased grain yield per plant. By selecting varieties with low expression levels of this gene or by mutating the gene through gene editing, superior cold-adapted rice varieties tolerant to low-temperature stress can be cultivated, showing promising application prospects.

The invention belongs to the field of biological medicine, and particularly relates to a qRT-PCR (quantitative reverse transcription-polymerase chain reaction) detection kit for rapid diagnosis of main subtypes of lung cancer as well as application and a detection method. The kit comprises a reverse transcription reagent and a PCR reaction reagent, the PCR reaction reagent comprises upstream and downstream primers of three spliceosomes of lung cancer related genes and upstream and downstream primers of reference genes, and the main subtypes of lung cancer are lung adenocarcinoma and lung squamous cell carcinoma. The invention discovers that the specificity of SOX30isform-2 is highly expressed in lung adenocarcinoma tissues for the first time; the specificity of SOX30isform-3 is highly expressed in lung squamous cell carcinoma tissues, so that the kit provided by the invention can quickly diagnose the lung cancer subtype, thereby formulating a precise treatment scheme and improving the early diagnosis and treatment efficiency.

The present disclosure provides engineered polynucleotides that interact with mRNA precursors and spliceosomes to modulate gene expression. The engineered polynucleotides may have a stem-loop structure with recruitment spliceosomes and a targeting sequence complementary to the target sequence at the exon-intron splice point, and may include nucleotides with 2'modifications and thiophosphate linkages The engineered polynucleotides may be administered to a subject to treat cancer.

The present disclosure provides novel pladienolide compounds according to Formula I:pharmaceutical compositions containing such compounds, and methods for using the compounds as therapeutic agents. These compounds may be useful in the treatment of cancer, particularly cancers in which agents that target the spliceosome and mutations therein are known to be useful. Also provided herein are methods of treating cancers by administering at least one compound disclosed herein and at least one additional therapy.

Provided is a method for preparing a circular RNA or chimeric RNA by means of an RNA self-splicing ribozyme or self-splicing pair. By means of a self-splicing reaction, both ends of two independent linear RNA molecules are respectively linked to each other to form a circular RNA molecule; or one end of one linear RNA molecule is linked to one end of the other independent RNA molecule to form a chimeric RNA molecule. The chemical modification levels of the two linear RNA molecules may be independently regulated, and then the two linear RNA molecules are linked to form a circular RNA or a chimeric RNA molecule, thereby achieving chemical modification with controllable modification types and modification levels for specific regions of the circular RNA molecule or the chimeric RNA molecule. The site-specific controllable RNA modification method can significantly improve the likelihood of RNAs becoming therapeutics and reduce toxic and side effects, thereby promoting the development of RNA vaccines and drugs.

This disclosure concerns an engineered polynucleotide that interacts with a pre-mRNA and a spliceosome to regulate gene expression. The engineered polynucleotide may have stem-loop structure that recruits the spliceosome and targeting sequences that are complementary to a target sequence at an exon-intron splice junction and may include nucleotides with 2′ modifications and phosphorothioate linkages. The engineered polynucleotide can be administered to a subject to treat a neurodegenerative disease.