Antisense Oligonucleotides for GLDC Exon Skipping
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cancer treatments are ineffective in selectively targeting glycine decarboxylase (GLDC) in cancer cells without affecting normal tissue, leading to adverse effects and limited therapeutic efficacy.
Innovation Solution
Development of antisense oligonucleotides that induce exon skipping of GLDC pre-mRNA or mature mRNA, specifically inhibiting GLDC expression by hybridizing to target regions, thereby inducing cell cycle arrest or apoptosis in GLDC-expressing cancer cells, using sequences selected from SEQ ID NOs: 1 to 94.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer treatments are used to target GLDC in cancer cells, then therapeutic efficacy is limited, but adverse effects occur due to lack of selectivity
Solution Approach 1:
The antisense oligonucleotide is designed with specific sequence complementarity to target only GLDC pre-mRNA or mature mRNA in cancer cells. The oligonucleotide binds to specific target regions (exons or introns) of GLDC RNA, inducing exon skipping or mRNA degradation locally at the target site, thereby achieving selective inhibition of GLDC expression in cancer cells without affecting normal tissue
Solution Approach 2:
The antisense oligonucleotide acts as an intermediary molecule that mediates the inhibition of GLDC expression. It hybridizes to GLDC pre-mRNA or mature mRNA, forming a DNA-RNA or RNA-RNA duplex that prevents proper RNA processing, splicing, or translation, thereby indirectly inhibiting GLDC protein synthesis in cancer cells
2Measurement precision
If antisense oligonucleotides are designed to induce exon skipping, then specificity to GLDC is improved, but mechanism complexity increases
Solution Approach 1:
The GLDC gene transcript is segmented into exons and introns, and the antisense oligonucleotide is designed to target specific segments (exons or introns) to induce exon skipping. By focusing on specific segments of the RNA molecule rather than the entire transcript, the oligonucleotide achieves high specificity while maintaining a relatively simple single-stranded structure
Solution Approach 2:
Instead of trying to directly inhibit GLDC protein function or block translation, the invention inverts the approach by targeting the pre-mRNA or mature mRNA level to induce exon skipping or mRNA degradation. This upstream intervention at the RNA processing stage achieves specificity through sequence complementarity while avoiding the complexity of protein-level inhibition
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 inhibit GLDC expression in cancer cells, leading to cell cycle arrest and apoptosis without adverse effects on normal tissue, demonstrating high specificity and therapeutic potential for cancers like non-small cell lung carcinoma and lymphomas.
Implementation Method 1
the oligonucleotide specifically hybridises to a target region of a GLDC pre-mRNA or mature mRNA
Data Source
Figure 1a~1d
Figure 2a~2c
Figure 3a~3d
AI summary
The present invention relates to antisense oligonucleotides for modulating the activity of glycine decarboxylase (GLDC). In particular, the present invention relates to antisense oligonucleotides capable of inducing exon skipping of RNA. Also claimed are pharmaceutical compositions, kits and methods of treating cancer and inducing exon-skipping using said antisense oligonucleotides. In addition, a method for aiding the categorising or determining prognosis of a cancer or in selecting a therapeutic strategy for a patient with cancer, based on assessing the level of GLDC nucleic acid, protein or activity in a sample derived from the patient is provided.