Antisense Oligonucleotides Targeting Natural Antisense Transcripts for BDNF Up-regulation
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Solution Overview
Problem
There is a need for continued development of oligonucleotides that effectively modulate BDNF protein expression to treat or research BDNF-related diseases, as existing technologies have limitations in targeting natural antisense transcripts for therapeutic utility.
Innovation Solution
The use of antisense oligonucleotides, siRNA, ribozymes, and small molecules that target specific regions of natural antisense transcripts to up-regulate or down-regulate BDNF sense gene expression in mammalian organisms, including patient cells or tissues, by contacting biological systems with oligonucleotides of specific sequences and lengths.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antisense oligonucleotides are used to target BDNF sense gene, then BDNF expression is down-regulated, but this limits therapeutic options for diseases requiring BDNF up-regulation
Solution Approach 1:
Instead of directly targeting the BDNF sense gene to down-regulate expression, the invention inverts the approach by targeting the natural antisense transcript (NAT) of BDNF. By designing oligonucleotides complementary to the NAT sequence, the therapy achieves up-regulation of BDNF sense gene expression, thereby expanding therapeutic options for diseases requiring increased BDNF levels.
2Reliability
If existing oligonucleotide technologies are used, then BDNF expression can be modulated, but they cannot effectively target natural antisense transcripts
Solution Approach 1:
The invention extends the functionality of oligonucleotide therapy by enabling targeting of natural antisense transcripts in addition to traditional sense gene targeting. This multi-functionality allows the same oligonucleotide technology platform to achieve both down-regulation (via sense gene targeting) and up-regulation (via NAT targeting) of BDNF expression, significantly expanding the therapeutic arsenal.
3Adaptability or versatility
If natural antisense transcripts are targeted, then BDNF sense gene expression is up-regulated, but new therapeutic approaches require continued development
Solution Approach 1:
The invention performs preliminary action by identifying and characterizing the natural antisense transcript sequences of BDNF, establishing a foundation for future therapeutic development. By pre-mapping the NAT sequences and designing complementary oligonucleotide sequences, the invention prepares the groundwork that simplifies subsequent drug development and manufacturing processes.
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
This approach effectively modulates BDNF expression and function, demonstrating increased neuronal outgrowth, survival, and proliferation, with potential therapeutic benefits for BDNF-related diseases.
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. Antisense nucleotides, for example, disrupt gene expression by hybridizing to target RNA
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 oligonucleotides that modulate the expression of and/or function of Brain derived neurotrophic factor (BDNF), in particular, by targeting natural antisense polynucleotides of Brain derived neurotrophic factor (BDNF). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of BDNF.