13 results about "Globin genes" patented technology

The present disclosure provides improved compositions for the homology directed repair of the human globin locus for the prevention, treatment, or amelioration of at least one symptom of a hemoglobinopathy.

Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDM1A, methods of increasing gamma globin gene expression, and methods to induce differentiation of cancer cells in a human or animal subject are also provided for the treatment of diseases such as acute myelogenous leukemia.

The invention belongs to the technical field of gene editing, and particularly relates to a method for reducing cell gene editing large fragment deletion. The invention provides a method for reducing cell gene editing large fragment deletion, which comprises the following steps: introducing a gene editing system into a cell, and carrying out gene editing on a gamma-globin gene promoter region so as to reduce HBG gene large fragment deletion, the gene editing system comprises Cas nuclease, gRNA and ssODN, the ssODN comprises a 5'homologous arm, a replacement sequence and a 3 'homologous arm, the length of the 5' homologous arm and the length of the 3 'homologous arm are respectively and independently 30-60 nt, and HBG gene large fragment deletion caused by multiple DSBs can be reduced by adjusting the length of the ssODN.

Methods of using one or more fumaric acid esters or pharmacologically active salts, derivatives, analogues, or prodrugs thereof to increase expression of fetal hemoglobin (HbF) are disclosed. The methods typically include administering to a subject an effective amount of one or more fumaric acid esters optionally in combination or alternation with hydroxyurea to induce HbF expression in the subject in an effective amount to reduce one or more symptoms of a sickle cell disorder, a hemoglobinopathy, or a beta-thalassemia, or to compensate for a genetic mutation is the human beta-globin gene (HBB) or an expression control sequence thereof. Pharmaceutical dosage units and dosage regimes for use in the disclosed methods are also provided.

This invention provides vectors (e.g., lentiviral vectors) and expression cassettes for incorporation into vectors for expressing an alpha-globin (α-globin) gene. In certain embodiments method of treatment using such vectors are provided.

One aspect of the invention is a method for amplifying alpha globin genes HBA1, HBA2 and HBA12 in a single PCR tube to determine an HBA genotype of a subject. This method employs five primers selected to accurate and sensitively identify the HBA1, HBA2, and HBA12, a gene found at a higher frequency in citizens of Saudi Arabia, by accurately annealing to nucleic acids in a biological sample and simultaneously amplifying sequences encoding the alpha globin genes. This invention includes a procedure and required reagents for the amplification of alpha globin genes in a single PCR tube.

The present invention relates to a polynucleotide construct comprising a hemoglobin subunit alpha-hemoglobin subunit beta (HBA-HBB) hybrid gene construct for enhancing the potency of gene therapy for the β-hemoglobinopathies, particularly β-thalassemia and sickle cell disease (SCD). The polynucleotide construct comprising elements that are operatively connected to each other in the following sequence: HBB locus control region (HBB-LCR), HBA promoter, and β-like globin gene. Additionally, the HBA-HBB gene construct further comprises a microRNA-based short hairpin RNA (shRNAmir) targeting one of the endogenous HBA or HBB genes to increase the ratio of vector-encoded HBBT87Q to endogenous HBA and β-like globin chains while maintaining high vector titers.

Disclosed herein are gene therapy vectors for efficient transduction of cells to express human beta globin genes. Specifically disclosed is an expression vector comprising: an expression cassette of a beta globin gene comprising an exon and an intron of a human beta globin gene, and a cis-acting element comprising one or more of WPRE, an SV40 polyadenylation signal and / or SV40 ori. The disclosed expression vectors have significantly enhanced viral vector packaging efficiency in viral vector packaging cell lines, which results in efficient integration of lentiviral vectors in target cells and high expression levels of beta globin genes. Pharmaceutical compositions and methods of treatment utilizing such expression vectors are also disclosed.

Provided herein are kits and methods for determining a thalassemia genotype of a subject. The present kit includes at least primers that target ζ2, Ψζ1, Ψα2, Ψα1, α2, α1 and θ1 genes in α-globin gene cluster, and primers that target variations in α2-globin gene and β-globin gene. Also encompasses herein is a method for determining a thalassemia genotype of a subject, in which gene copy number of each target sites in ζ2, Ψζ1, Ψα2, Ψα1, α2, α1 and θ1 genes in α-globin gene cluster are determined by use of the present kit, and compared with those of normal or known thalassemia subject to arrive at the thalassemia genotype of the subject.

The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.

The invention relates to the technical field of animal breeding, in particular to an expression vector based on a bovine-derived K5 gene and application of the expression vector. The expression vector comprises an expression cassette, wherein the expression cassette comprises a 5'end regulation region of a bovine-derived K5 gene, an intron of a beta-globin gene, a target gene and a 3 'end regulation region of the bovine-derived K5 gene. An expression vector based on a bovine-derived K5 gene regulatory region and a beta-globin gene intron is obtained through research and used for specific expression in pig skin cells, and then a pig variety with specific characters is obtained through cultivation. Based on the expression vector, the pig with the black skin character is successfully prepared.

The present invention provides an application of thyroid hormones and thyroid hormone analogues to preparation of drugs for treating sickle-cell disease, particularly an application to preparation of drugs for improving the expression quantity of ζ-globin. During the differentiation of K562 cells, thyroid hormone analogue (Triac) can significantly up-regulate the expression of ζglobin gene (HBZ) by 50 folds or above. The expression of ζ-globin gene (hbae5) can also be up-regulated by 30-70 folds in zebrafish treated with thyroid hormones and thyroid hormone analogues. Therefore, according to the present invention, the expression of ζ-globin gene can be significantly activated by thyroid hormones and thyroid hormone analogues which may develop new potential therapies for patients with sickle-cell disease. It provides an economical, safe and effective method for treating sickle-cell disease and can be widely used.

The invention is applicable to the technical field of biology, and provides a primer probe combination, a kit and a method for detecting high-risk human papilloma virus nucleic acid, a specific detection system is designed aiming at 18 high-risk HPVs, the system comprises a specific primer pair, a fluorescent probe, a nucleic acid extraction reagent and a PCR reaction reagent, a Beta-Globin gene is used as a reference gene, and the specific primer pair and the fluorescent probe are used for detecting the high-risk human papilloma virus nucleic acid. According to the invention, the number of primers is reduced through base merging design, primer dimer, mismatch and nonspecific binding are avoided, and specific typing of HPV16 and HPV18 and qualitative detection of other 16 high-risk HPVs are realized in combination with a multiplex fluorescent PCR technology; meanwhile, the reagent concentration and the PCR amplification procedure are optimized, and the kit has the advantages of being high in detection specificity, high in sensitivity, easy and convenient to operate, low in cost and high in clinical accuracy rate, can be effectively used for in-vitro qualitative detection of the high-risk HPV in a cervical exfoliated epithelial cell sample, and provides a reliable basis for early screening of cervical cancer.