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

Modulators of apol1 expression

A technology of -O-2 and oligonucleotide, which is applied in the direction of recombinant DNA technology, DNA/RNA fragments, medical preparations containing active ingredients, etc., can solve the problem that the disease cannot be completely prevented from progressing, so as to slow down the progress and achieve high The effect of therapeutic value

Pending Publication Date: 2021-02-26
IONIS PHARMA INC
View PDF91 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Antihypertensive and anti-inflammatory treatments have been found to slow progression and reduce symptoms in some types of chronic kidney disease (CKD), but they neither cause disease regression nor completely halt disease progression

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
  • Modulators of apol1 expression
  • Modulators of apol1 expression
  • Modulators of apol1 expression

Examples

Experimental program
Comparison scheme
Effect test

example

[0356] The following example describes the screening process used to identify lead compounds targeting APOL1. For example, ION793406, 904763, 905469, 905505, 905634, 905665, 972190 and 972163 resulted in high potency and tolerability. ION 972190 exhibited high potency and tolerability.

[0357] Non-limiting disclosure and incorporation by reference

[0358]Although the sequence listing accompanying this document identifies each sequence as "RNA" or "DNA" as appropriate, in practice those sequences may be modified with any combination of chemical modifications. Those skilled in the art will readily recognize that terms such as "RNA" or "DNA" to describe modified oligonucleotides are in some cases arbitrary. For example, an oligonucleotide comprising a nucleoside containing a 2'-OH sugar moiety and a thymine base can be described as DNA with a modified sugar (2'-OH for the natural 2'-H of DNA) or as having RNA with modified bases (thymine (methylated uracil) for RNA's natural...

example 1

[0363] Example 1: Antisense inhibition of human APOL1 in A431 cells

[0364] Antisense oligonucleotides with various chemical motifs targeting APOL1 nucleic acids were designed and tested for their effect on APOL1 mRNA in vitro.

[0365] 3-10-3 cEt Notch body

[0366] The newly designed chimeric antisense oligonucleotides in the table below were designed as 3-10-3 cEt gapmers. These gap bodies are 16 nucleosides long, with a central gap segment consisting of ten 2'-deoxynucleosides and flanked in the 5' and 3' directions by wing segments each comprising three nucleosides . Every nucleoside in the 5' wing segment and every nucleoside in the 3' wing segment has a cEt modification. The internucleoside linkages throughout each notch body are phosphorothioate (P=S) linkages. All cytosine residues throughout each notch body are 5-methylcytosine.

[0367] "Start site" indicates the most 5' nucleoside in the human gene sequence to which the Notch body is targeted. "Stop site" ...

example 2

[0554] Example 2: Dose-dependent antisense inhibition of human APOL1 in A431 cells

[0555] Notchsomes from Example 1 that exhibited significant APOL1 mRNA suppression in vitro were selected and tested in A431 cells at different doses. These antisense oligonucleotides were tested in a series of experiments with similar culture conditions. The results of each experiment are presented in a separate table as shown below.

[0556] Cells were plated at a density of 10,000 cells per well and transfected with free uptake of 3-10-3cEt Notchsome at various concentrations as indicated in the table below. After a treatment period of approximately 16 hours, RNA was isolated from the cells and APOL1 mRNA levels were measured by quantitative real-time PCR. The human primer probe set RTS35962 was used to measure mRNA levels. as passed For measurements, APOL1 mRNA levels were adjusted for total RNA content. Results are presented as percent inhibition of APOL1 relative to untreated contr...

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 present embodiments provide methods, compounds, and compositions useful for inhibiting APOL1 expression, which may be useful for treating, preventing, or ameliorating a disease associated with APOL1.

Description

[0001] sequence listing [0002] This application is filed together with a Sequence Listing in electronic format. The sequence listing is provided as a file titled 200779-WO-PCT-SeqListingUpdated.txt created on May 20, 2019, which is 465 kb in size. The information of the sequence listing in electronic format is hereby incorporated by reference in its entirety. technical field [0003] This example provides methods, compounds, and compositions that can be used to inhibit the expression of APOL1 (apolipoprotein L, 1), and in some cases reduce the amount of APOL1 protein in cells or animals. These methods, compounds, and combinations The substances can be used for treating, preventing, or alleviating diseases related to APOL1. Background technique [0004] End-stage kidney disease (ESKD) affects more than half a million individuals in the United States. In the United States, individuals of African ancestry were approximately twice as likely to develop ESKD as those observe...

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): A61K48/00C07H21/02
CPCA61P13/02C12N15/113C12N2310/11C12N2310/341C12N2310/315C12N2310/346C12N2320/30C12N2310/3231A61K31/7088C12N2310/321C12N2310/3525C12N2310/3341C12N2320/32C12N2320/35A61K48/00
Inventor S·M·弗雷尔
Owner IONIS PHARMA INC
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