Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Oligonucleotide and its derivatives, and applications thereof

A technology of oligonucleotides and derivatives, applied in the field of oligonucleotides and derivatives thereof, can solve problems such as functional effects

Inactive Publication Date: 2014-01-01
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] All-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia can greatly improve the complete remission rate and survival rate of patients, and is currently an effective clinical treatment. These drugs can cause fusion protein degradation or cell differentiation after treatment Termination, which can lead to a decrease in tissue factor, but these drug treatments may affect other signaling pathways or regulatory mechanisms of cells and other functions of cells and in vivo

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
  • Oligonucleotide and its derivatives, and applications thereof
  • Oligonucleotide and its derivatives, and applications thereof
  • Oligonucleotide and its derivatives, and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1 , Synthesis of oligonucleotides

[0040] Artificially synthesized sense strand (5'-cagctccgcgctcggtgg-3') with full-chain phosphorothioated modification and FITC-labeled at the 5' end, and synthesized antisense with full-chain phosphorothioated modification strand (5'-ccaccgagcgcggagctg-3'), which forms a double-stranded oligonucleotide molecule after annealing.

[0041] At the same time, artificially synthesized double-stranded oligonucleotide modifications with the deletion of the middle four bases gctc and the mutation of the middle three bases ctc to aaa were used as controls (-237~-235 mutation and -238~-235 deletion).

[0042] It is easy to understand that although this example only lists oligonucleotides modified by phosphorothioation, other similar modification methods are used for modification, such as methylphosphoramide modification, stem-loop modification, dumbbell-shaped closure modification, etc. The purpose of avoiding enzymatic degradation i...

Embodiment 2

[0043] Example 2 , oligonucleotide transfection

[0044] The artificially synthesized oligonucleotides in Example 1 were transfected into NB4 cells, U937-PR9 cells, and U937-PR9 cells plus Zn 2+ In the control group, cells were directly electroporated without adding oligonucleotides as a blank control. Among them, U937-PR9 cells plus Zn 2+ The control group was treated as follows: Zn was added 4, 12, and 24 hours before the cells were collected. 2+ Induce fusion protein production.

[0045] The specific steps of transfection are as follows:

[0046] After brief centrifugation of the freeze-dried powder of oligonucleotide synthesis products, the RPMI-1640 medium was used to prepare a storage concentration of 100 pmol / μl. Count 4×10 6 After washing by centrifugation, resuspend with 90 μl RPMI-1640 medium, add appropriate amount of oligonucleotide storage solution, mix gently, transfer to Cell Line Kit V electroporation cup, electroporation final concentration is 0.1μM...

Embodiment 3

[0047] Example 3 , Detection of oligonucleotide transfection efficiency

[0048] 3.1. Flow cytometry detection

[0049] Flow cytometry was used to detect the positive percentage of FITC in U937-PR9 cells electroporated with and without oligonucleotides in Example 2, as an index for evaluating electrotransfection efficiency.

[0050] The detection steps are as follows: collect U937-PR9 cells 24 hours after electroporation of oligonucleotides, absorb an appropriate amount of cells, discard the supernatant after centrifugation, wash once with RPMI-1640 medium, then resuspend with 400 μl RPMI-1640 medium, and carry out FITC efficiency was detected by flow cytometry to monitor the electrotransfection efficiency of FITC-labeled oligonucleotides.

[0051] The result is as figure 1 A and figure 1 As shown in B, the solid line represents the blank control without oligonucleotide electroporation of cells directly, and the dotted line represents the experimental group of oligonucleo...

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 provides an oligonucleotide (5'-cagctccgcgctcggtgg-3') capable of reducing the high expression of a PML / RARalpha fusion protein related tissue factor (TF), and its derivatives, and applications of the oligonucleotide (5'-cagctccgcgctcggtgg-3') and its derivatives in the prevention and / or treatment of acute leukemia and its complications and / or other PML / RARalpha related tissue factor abnormal-high-expression or its acceptor activity abnormal-change related diseases, and / or the improvement of TF high-expression related pathology phenomena, such as coagulopathy.

Description

technical field [0001] The invention belongs to the technical field of cell bioengineering, and in particular relates to an oligonucleotide and its derivatives and their application. Background technique [0002] Many patients with hematological malignancies often have obvious abnormal bleeding and coagulation signs in clinical practice. The reason is that in addition to platelet abnormalities, there are complex coagulation abnormalities (Tallman MS, Kwaan HC, Rev Clin Exp Hematol, 8( 1), E1, 2004; Nadir Y, Katz T, Sarig G, et al. Haematologica, 90(11), 1549-1556, 2005). Acute leukemia is often associated with coagulation dysfunction, and complications such as bleeding and thrombus are prone to occur. The abnormality of the coagulation system in acute leukemia is related to various factors such as the increased expression of tissue factor (Tissue Factor, TF) and the release of tumor procoagulant substances. The increased expression of TF is considered to be one of the main...

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
IPC IPC(8): C12N15/113A61K48/00A61P35/00A61P35/02A61P35/04
Inventor 奚晓东
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com