Dual Target Nucleic Acid Molecule Design for Cancer Therapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Designing dual target nucleic acid molecules that can effectively target multiple genes related to the same disease is challenging due to sequence diversity and the risk of off-target effects, particularly in cancer therapy where controlling one gene is insufficient and resistance to anticancer drugs often develops.
Innovation Solution
A method involving the extraction of gene sequences from a database, segmentation, alignment, and scoring to design siRNA or shRNA molecules that target specific genes, using a weighted scoring system to optimize sequence characteristics and prevent off-target effects, with one strand targeting a first gene and another strand targeting a second gene related to the same disease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If one designs nucleic acid molecules to target multiple genes simultaneously, then therapeutic efficacy is improved, but the risk of off-target effects increases
Solution Approach 1:
The nucleic acid molecule is divided into multiple distinct binding regions, each targeting a different gene. Each region is optimized independently to ensure specific binding to its target while minimizing cross-interference with other targets, thereby reducing off-target effects while maintaining multi-gene targeting capability
Solution Approach 2:
The design optimizes specific parameters including GC content (30-70%), melting temperature (18-24°C), and sequence composition to enhance binding specificity. By carefully controlling these parameters, the molecule achieves high affinity for target genes while reducing non-specific binding to off-target sequences
2Reliability
If the nucleic acid sequence is optimized for high binding affinity, then gene expression inhibition is improved, but the specificity decreases
Solution Approach 1:
Different regions of the nucleic acid molecule have different sequence characteristics optimized for their specific functions. The binding regions have high GC content for strong binding, while spacer regions have lower complexity to reduce secondary structure formation. This local optimization allows high affinity binding without sacrificing overall specificity
Solution Approach 2:
The design process incorporates iterative optimization where binding affinity and specificity are evaluated together. Computational algorithms predict both the strength of target binding and the likelihood of off-target interactions, allowing adjustments to sequence composition to achieve the optimal balance between these two competing requirements
3Reliability
If multiple nucleic acid molecules are delivered separately, then each target gene can be precisely controlled, but the delivery complexity and off-target effects increase
Solution Approach 1:
Multiple nucleic acid sequences targeting different genes are merged into a single polynucleotide molecule with defined secondary structure. This consolidation simplifies delivery by requiring only one molecule to be introduced into cells, while maintaining the ability to specifically control multiple target genes through the distinct binding regions within the molecule
Solution Approach 2:
The single nucleic acid molecule performs multiple functions by containing multiple independent binding regions. Each region can independently bind to its target gene sequence, allowing the molecule to simultaneously regulate expression of multiple genes involved in the same disease pathway, thereby achieving multi-target therapy with a single agent
Data Source
AI summary
Disclosed is a method comprising extracting a gene sequence of a first gene from a first database in response to receiving a user's input, generating segmented sequences on the basis of the reverse complementary sequence of the gene sequence of the first gene, identifying, based on comparison of the segmented sequences with gene sequences of a second database, at least one matched sequence corresponding to at least one segmented sequence of the segmented sequences.