Oligomers with improved off-target profile

A technology of oligomers and monomers, applied in the field of oligomers and oligonucleotides

A technology of oligomers and monomers, applied in the field of oligomers and oligonucleotides

CN104955950AActive Publication Date: 2015-09-30GUANGDONG MAIJINJIA BIOTECH CO LTD
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  • Oligomers with improved off-target profile
  • Oligomers with improved off-target profile
  • Oligomers with improved off-target profile

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0176] In this example, the affinity of various oligos to the target of interest as well as to off-target RNA was measured. Finally, the affinity of the oligos to the target RNA consisting of the consensus sequence is measured.

[0177] The target RNA used was first:

[0178] (135-Hcvtarg)5'GAUGGGGGCG ACACUCCA CCAUGAAU

[0179] where the consensus sequence is underlined.

[0180] Sequence of the oligomer complementary to the target RNA:

[0181] CUGUGAGGUGGUAC-5'

[0182] and when combined with each other:

[0183] Target: 5'GAUGGGGGCG ACACUCCA CCAUGAAU

[0184] |||||||||||||||

[0185] HCV oligomer CUGUGAGGUGGUAC5'

[0186] First, use the following oligos, where the lower affinity region is underlined:

[0187] (123-HCVtm, uniformly modified):

[0188] lClAmUmGlGmUlGlGmAlGmUmGlTlC

[0189] (124-HCVtm, lower affinity region complementary to the consensus sequence):

[0190] lClAlTlGlGlT mGmGmAmGmUm GlUlC

[0191] (125-HCV, lower affinity regio...

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Abstract

The present invention provides oligomers that binds RNA that consists of a lower affinity region and a higher affinity region, wherein the monomers in the higher affinity region increases the melting temperature (i.e. affinity) of the oligomer base paired to RNA more than the monomers used in the lower affinity region, wherein said increase in melting temperature is relatively to the alternative use of DNA monomers of the same (base) sequence. The oligomers of the invention are useful for binding to target RNA such as mRNA and non-coding RNA and have the advantage that they will be less prone to off-target binding via the lower affinity region than via the higher affinity region.

Description

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Claims

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Application Information

Patent Timeline
30 Sep 2015
Publication
CN104955950A