Antisense Oligonucleotide Targeting MBTPS1 Natural Antisense Transcript
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Solution Overview
Problem
Current methods for modulating the expression and function of MBTPS1 polynucleotides are limited in their ability to specifically target and regulate the natural antisense transcripts, leading to incomplete or inefficient modulation of gene expression.
Innovation Solution
The use of antisense oligonucleotides, specifically designed to have at least 50% sequence identity to a reverse complement of a polynucleotide within a defined region of the MBTPS1 sequence, is employed to inhibit natural antisense transcripts, thereby up-regulating the corresponding sense gene. These oligonucleotides can be administered subcutaneously, intramuscularly, or intravenously and may include modified nucleotides such as phosphorothioate or locked nucleic acids, and can be encapsulated in liposomes or attached to carrier molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional methods are used to modulate MBTPS1 expression, then general gene expression modulation is achieved, but specific targeting of natural antisense transcripts is insufficient
Solution Approach 1:
The invention segments the MBTPS1 gene regulation by specifically targeting the natural antisense transcript (NAT) rather than treating the sense and antisense strands equally. The antisense oligonucleotide is designed to specifically hybridize to the NAT sequence, separating the regulation of the sense gene from the antisense interference, thereby achieving precise control over MBTPS1 expression.
Solution Approach 2:
Instead of directly targeting the sense MBTPS1 transcript for suppression (conventional approach), the invention takes the opposite strategy by targeting the natural antisense transcript for suppression. This inversion allows the sense gene to be up-regulated indirectly through relief of antisense-mediated repression, achieving more effective and specific gene modulation.
2Measurement precision
If antisense oligonucleotides are designed with high sequence identity to reverse complement, then specific binding to natural antisense transcripts is achieved, but oligonucleotide design complexity increases
Solution Approach 1:
The invention performs preliminary sequence analysis and design by identifying the natural antisense transcript sequence first, then designing the antisense oligonucleotide to complement this pre-identified sequence. This preliminary characterization of the NAT allows for systematic design of effective oligonucleotides without trial-and-error complexity.
Solution Approach 2:
The invention optimizes the sequence identity parameter of the antisense oligonucleotide to at least 50% identity to the reverse complement of the NAT. This specific parameter threshold balances binding specificity with design simplicity, allowing for effective targeting while maintaining manageable oligonucleotide design complexity through defined sequence requirements.
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 approach effectively modulates the expression and function of MBTPS1 polynucleotides by specifically targeting and inhibiting natural antisense transcripts, demonstrating significant up-regulation of MBTPS1 mRNA levels in cell treatments, as shown in real-time PCR results, indicating a robust and specific regulatory mechanism.
Implementation Method 1
DNA-RNA and RNA-RNA hybridization are important to many aspects of nucleic acid function including DNA replication, transcription, and translation. Hybridization is also central to a variety of technologies that either detect a particular nucleic acid or alter its expression.
Implementation Method 2
Antisense DNA has the added feature that DNA-RNA hybrids serve as a substrate for digestion by ribonuclease H, an activity that is present in most cell types.
Data Source
AI summary
The present invention relates to antisense oligonuclotides that modulate the expression of and/or function of Membrane Bound Transcription Factor Peptidase, site 1 (MBTPS1), in particular, by targeting natural antisense polynucleotides of Membrane Bound Transcription Factor Peptidase, site 1 (MBTPS1). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of MBTPS1.