Conserved Oligonucleotides for Universal HIV Gene Silencing
Solution Overview
Problem
Current RNA interference approaches targeting HIV are ineffective due to the high mutation frequency of the HIV genome, making it difficult to develop a universal gene therapy for AIDS.
Innovation Solution
Development of conserved oligonucleotide sequences derived from HIV genome homology alignment, which can be used to create single-strand or double-strand RNA, hairpin RNA, and DNA sequences to knock down HIV gene expression, along with expression vectors and liposomes for delivery into cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional RNA interference approaches targeting HIV are used, then gene expression can be knocked down in specific isolates, but the high mutation frequency of HIV genome makes it ineffective as a universal approach
Solution Approach 1:
The patent applies universality by designing RNA interference sequences that simultaneously target multiple highly conserved regions of the HIV genome (such as gag, pol, env genes). This multi-target approach ensures that the therapy remains effective across different HIV isolates and mutants, as the high conservation of these regions means they are less prone to mutation. The single therapeutic intervention thus achieves universal applicability against diverse HIV strains.
Solution Approach 2:
The patent applies local quality by specifically selecting highly conserved regions of the HIV genome as targets for RNA interference. These conserved regions (such as specific sequences in gag, pol, and env genes) have critical functional importance and exhibit low mutation rates compared to other parts of the viral genome. By focusing the interference action on these specific local regions with unique properties (high conservation), the therapy achieves both reliability and universality.
2Reliability
If RNA sequences are introduced to knock down HIV gene expression, then viral gene expression can be suppressed, but drug resistant problems arise from genomic mutagenesis
Solution Approach 1:
The patent applies segmentation by dividing the HIV genome into multiple distinct conserved regions (gag, pol, env, and other functional domains) and designing separate RNA interference sequences for each region. Instead of relying on a single target, the therapy uses multiple segmented targets throughout the viral genome. This segmentation strategy ensures that mutations in one region do not confer resistance, as the other segmented targets remain intact and continue to be suppressed by their corresponding RNA sequences.
Solution Approach 2:
The patent applies parameter changes by targeting multiple different parameters (conserved sequences) across the HIV genome rather than a single parameter. By selecting targets based on their conservation levels, functional importance, and sequence variability, the patent creates a multi-parameter approach where the therapeutic effect is distributed across several genomic locations. This reduces the probability of resistance development, as simultaneous mutations in multiple conserved regions are highly unlikely.
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
These sequences significantly decrease HIV gene expression and genome degradation, reducing drug-resistant problems and providing a universal approach for HIV prevention and treatment.
Implementation Method 1
double strand RNA derived by annealing of the sequences with its complements sequences
Implementation Method 2
the hairpin sequences were derived by the hybridization of the sequences (SEQ ID No. 1 ∼SEQ ID No. 9) or the relevant segments at 5′ terminal with their complement sequences
Data Source
AI summary
The invention provides a group of nucleic acid fragments, shown in the sequence listing, for prevention of HIV infection or AIDS and the usage thereof. In the invention, a series of RNA fragments, which are highly homogenous to all the published HIV gene sequences, were obtained by homology compare. The double-stranded RNA (dsRNA) derived from these fragments can effectively inhibit the expression of the HIV genes. The RNA transcribed by plasmid, also can suppress the expression of the HIV in the cell. After the adenovirus or associated virus which carry DNA corresponding above RNA infect the cell, the transcription dsRNA can inhibit the expression of the HIV genes.