Lentiviral vector suitable for gene therapy of thalassemia and sickle anemia

A technology of lentiviral vector and gene locus, which is applied in the medical field, can solve the problem of virus titer reduction and other problems, and achieve the effect of preventing gene activation and maintaining gene expression

Active Publication Date: 2019-12-13
SHANGHAI BDGENE TECH CO LTD
View PDF2 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, a mini-locus (miniLCR) consisting of core elements of HS4, HS3, HS2 deoxyribonuclease I hypersensitive sites resulted in a significant reduction in viral titer (Weber, L. et al. AnOptimized Lentiviral Vector Efficiently Corrects the Human Sickle Cell Disease Phenotype. Mol The Methods Clin Dev 10, 268-280 (2018)

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Lentiviral vector suitable for gene therapy of thalassemia and sickle anemia
  • Lentiviral vector suitable for gene therapy of thalassemia and sickle anemia
  • Lentiviral vector suitable for gene therapy of thalassemia and sickle anemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] The present invention screens an expression box of human beta globin with red blood cell specificity and high-efficiency expression, and then obtains a lentiviral vector containing the expression box for gene therapy. Carrier design such as figure 1 As shown, the expression cassette comprises the following elements: (1) mini-locus control region (miniLCR), that is, a length 3kb (sequence such as shown in SEQ ID NO.1) or 2.6kb (sequence shown in SEQ ID NO.2) regulatory element; (2) gene sequence of beta globin (sequence shown in SEQ ID NO.3); Son 2 contained the T87Q mutation. (3) 265-bp beta globin gene sequence upstream promoter sequence (sequence shown in SEQ ID NO.4); (4) downstream 300-bp beta globin gene sequence polyA sequence (sequence as SEQ ID shown in NO.5). Place the expression cassette in a lentiviral vector. The sequence of the lentiviral vector containing the 3kb minilocus control region is shown in SEQ ID NO.7. The sequence of the lentiviral vector c...

Embodiment 2

[0041] The present invention screens an expression box of human beta globin with red blood cell specificity and high-efficiency expression, and then obtains a lentiviral vector containing the expression box for gene therapy. Carrier design such as figure 1 As shown, the expression cassette comprises the following elements: (1) mini-locus control region (miniLCR), that is, a length 3kb (sequence such as SEQ ID NO.1) or a 2.6kb (sequence shown in SEQ ID NO.2) regulatory element; (2) the complete beta globin gene sequence. Among them, exon 2 contains T87Q mutation. (3) 265-bp beta globin gene sequence upstream promoter sequence (sequence shown in SEQ ID NO.4); (4) downstream 300-bp beta globin gene sequence polyA sequence (sequence as SEQ ID shown in NO.5). This expression cassette is placed in a lentiviral vector, which selectively adds the insulator sequence. In the case of adding an insulator sequence, a 36bp insulator sequence from Foamy virus (sequence shown in SEQ ID NO...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses a lentiviral vector suitable for gene therapy of thalassemia and sickle anemia. The lentiviral vector comprises a beta globin expression cassette; the expression cassette comprises a micro-locus control area, a gene sequence of a beta globin, a promoter sequence of a flank of the upstream of the gene sequence of the beta globin, and a flanking sequence of the downstream ofthe gene sequence of the beta globin; the micro-locus control area is a micro-control element which is screened out from the locus control area of beta globin 16kb and does not contain an HS1 area. Compared with the prior art, the screened beta globin expression cassette has both efficiency and specificity, and does not cause reduction of lentivirus titer; a screened insulator sequence which comesfrom foamy virus and is only 36 bp does not contain a hidden RNA splicing signal, and has the functions of maintaining gene expression and preventing gene activation in a region where the insulator sequence is located; the lentiviral vector can be used for gene therapy of thalassemia and sickle anemia.

Description

technical field [0001] The invention belongs to the field of medical technology, and in particular relates to a lentiviral vector suitable for gene therapy of thalassemia and sickle-cell anemia. Background technique [0002] So far, more than 7,000 rare diseases have been discovered in humans, but only 5% of the rare diseases have drugs available. Currently, almost all rare disease drugs require lifelong use. Gene therapy offers the possibility of a one-time cure for rare diseases. Thalassemia (thalassemia) is a monogenic hereditary hemoglobinopathy with the widest distribution and the largest cumulative patient population in the world. It is the most common human hereditary disease among rare diseases. [0003] The safety of gene therapy is the premise that it can become a routine therapy and benefit more patients. Lentiviral vectors are inserted into the genome in an uncontrolled manner (about 75% are integrated into transcriptionally active gene coding regions), accomp...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/867C12N15/12A61K48/00A61P7/06
CPCA61K48/0008A61P7/06C07K14/805C12N15/86C12N2740/15043C12N2830/40C12N2830/60
Inventor 汪啸渊徐婷
Owner SHANGHAI BDGENE TECH CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap