Antisense Oligonucleotides Inducing PRDM15 Exon Skipping for Cancer Therapy
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Solution Overview
Problem
Current treatments for cancers overexpressing PR-domain containing protein 15 (PRDM15) lack effective and selective targeting methods, as small molecule inhibitors have not been identified, and existing therapies may have adverse effects on normal tissues.
Innovation Solution
Development of antisense oligonucleotides that specifically inhibit PRDM15 expression by inducing exon skipping of PRDM15 pre-mRNA or mature mRNA, leading to cell cycle arrest and apoptosis in cancer cells, with no adverse effects on normal tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing cancer therapies are used to treat PRDM15-overexpressing cancers, then cancer cells may be affected, but normal tissues suffer adverse effects
Solution Approach 1:
The patent uses antisense oligonucleotides as intermediary molecules that specifically bind to PRDM15 pre-mRNA to induce exon skipping. This intermediary approach allows selective targeting of the PRDM15 gene expression pathway in cancer cells without directly affecting normal tissues, thereby resolving the contradiction between treatment effectiveness and safety.
Solution Approach 2:
The invention applies local quality by designing oligonucleotides with specific sequences (SEQ ID NOs: 18, 19, 21, 26, 27, 36, 70, 71, 72, 73) that target only the PRDM15 pre-mRNA molecule at specific exon regions. This localized targeting ensures that only the intended gene expression is affected in cancer cells, leaving normal tissues unaffected.
2Reliability
If small molecule inhibitors are developed to target PRDM15, then selective inhibition may be achieved, but such inhibitors have not been identified yet
Solution Approach 1:
The patent replaces the hypothetical small molecule inhibitor approach with an oligonucleotide-based mechanism. Instead of using small molecules that would require extensive screening and development, the invention uses chemically synthesized oligonucleotides with defined sequences that can be more readily manufactured and have predictable binding behavior to the PRDM15 pre-mRNA target.
3Productivity
If PRDM15 expression is completely deleted to treat cancer, then cancer cell growth is inhibited, but normal tissue function may be compromised
Solution Approach 1:
The patent applies partial action by inducing exon skipping that reduces PRDM15 protein expression to a level sufficient to inhibit cancer cell proliferation but not so complete as to compromise normal tissue function. The oligonucleotides achieve partial depletion of PRDM15, which is therapeutic for cancer while sparing normal tissues that require minimal PRDM15 for homeostasis.
4Measurement precision
If oligonucleotides are designed to induce exon skipping of PRDM15 pre-mRNA, then specific hybridization to target region is achieved, but only certain sequence variants are effective
Solution Approach 1:
The patent achieves universality by designing oligonucleotide sequences that can bind to conserved regions of the PRDM15 pre-mRNA across different cancer types and potentially different genetic variants. The selected sequences (SEQ ID NOs: 18, 19, 21, 26, 27, 36, 70, 71, 72, 73) are chosen to target regions that are likely to be conserved, allowing the same oligonucleotides to be effective across multiple PRDM15-overexpressing cancer types including lymphomas, glioblastoma, breast, prostate, lung and colon cancers.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The antisense oligonucleotides effectively induce cell cycle arrest and apoptosis in PRDM15-overexpressing cancer cells while maintaining normal tissue homeostasis, providing a novel and selective therapeutic approach for PRDM15-expressing cancers.
Implementation Method 1
the antisense oligonucleotide has any one sequence selected from SEQ ID NOs: 18, 19, 21, 26, 27, 36, 70, 71, 72 and 73, which specifically hybridises to a target region of a PRDM15 pre-mRNA or mature mRNA
Data Source
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AI summary
The present invention relates to antisense oligonucleotides for modulating the activity of PRDM15 and use thereof in the treatment of cancer. In particular, said antisense oligonucleotides are capable of inducing the skipping of an exon of a PRDM15 mRNA. The present invention also relates to a method for determining prognosis in a patient with cancer, or selecting a therapeutic strategy for a patient with cancer, by assessing the level of PRDM15 nucleic acid, protein or activity in a sample.