PPIF Antisense Oligomers for Selective CYPD Splicing Modulation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for diseases and pathologies associated with Cyclophilin D (CYPD) are limited by the non-specific modulation of cyclophilin proteins, leading to unwanted effects on beneficial cyclophilin members, and there is a need for targeted methods to modulate CYPD levels in specific tissues and the body.
Innovation Solution
The use of antisense oligomers that target the PPIF gene transcript to induce non-productive splicing, specifically inducing exon skipping and terminal intron retention, thereby reducing CYPD protein expression and function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pan-cyclophilin inhibitors such as cyclosporin A are used to treat CYPD associated diseases, then CYPD protein function is inhibited, but other beneficial cyclophilin members are also inactivated
Solution Approach 1:
The invention segments the cyclophilin family by targeting specifically the PPIF gene (encoding CYPD) rather than all cyclophilin members. The antisense oligomer is designed to bind specifically to PPIF pre-mRNA, enabling selective modulation of CYPD while preserving other cyclophilin family members with beneficial functions.
Solution Approach 2:
The invention applies local quality by designing the antisense oligomer with a specific targeting sequence complementary to a unique region in the PPIF gene transcript. This local specificity ensures that only CYPD expression is modulated, while other cyclophilin proteins remain unaffected, thereby eliminating off-target effects.
2Reliability
If naturally occurring immunosuppressive drugs are used to modulate CYPD, then disease symptoms are reduced, but the treatment approach is non-specific and lacks tissue targeting capability
Solution Approach 1:
The invention uses an intermediary approach by employing antisense oligomers as mediators that can be delivered to specific tissues. These oligomers serve as targeted intermediaries that modulate CYPD expression locally in affected tissues rather than systemically, enabling tissue-specific treatment and improving therapeutic efficacy while minimizing side effects.
3Quantity of substance
If existing treatments are used to reduce CYPD levels, then protein function is inhibited, but the methods cannot selectively modulate CYPD in specific tissues
Solution Approach 1:
The invention introduces dynamics by enabling controllable and adjustable modulation of CYPD levels in specific tissues. The antisense oligomer treatment can be administered at different doses and frequencies, allowing dynamic control over the extent of CYPD reduction in target tissues while maintaining normal levels in other tissues.
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 CYPD expression by generating non-functional protein isoforms, reducing overall protein function and minimizing off-target effects, providing therapeutic benefits for diseases related to CYPD.
Implementation Method 1
an antisense oligomer of 10 to 50 nucleotides comprising a targeting sequence complementary to a region near or within an intron of the PPIF gene transcript
Data Source
AI summary
An isolated or purified antisense oligomer which has a modified backbone structure for modifying pre-mRNA splicing in the PPIF gene transcript or part thereof.