CIDEB-Targeting dsRNA With Lipid Delivery and Stability Tuning
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Solution Overview
Problem
There is a need for compositions and methods to treat diseases and disorders associated with the activity of cell death-inducing DFFA-like effector B (CIDEB), particularly in conditions such as non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), which are prevalent due to metabolic syndrome and lifestyle changes.
Innovation Solution
The use of double-stranded RNA (dsRNA) to inhibit the expression of CIDEB through RNA interference mechanisms, including specific sense and antisense strands, optionally with modifications and conjugation to ligands, to reduce CIDEB activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dsRNA is used to inhibit CIDEB expression, then therapeutic benefit is improved, but delivery efficiency and stability in vivo are worsened
Solution Approach 1:
The patent uses lipids as intermediary carriers to deliver dsRNA into cells. The lipids form liposomes that encapsulate dsRNA and facilitate its entry into target cells through membrane fusion, overcoming the delivery efficiency problem while maintaining therapeutic benefit.
Solution Approach 2:
The patent modifies the chemical structure of dsRNA by incorporating modified nucleotides with different chemical properties. These parameter changes in nucleotide structure improve dsRNA stability, reduce degradation, and enhance cellular uptake, thereby improving delivery efficiency while preserving therapeutic effect.
2Reliability
If dsRNA is used to inhibit CIDEB expression, then therapeutic benefit is improved, but dsRNA stability and resistance to degradation are worsened
Solution Approach 1:
The patent employs modified nucleotides that change the chemical parameters of dsRNA. These modifications include altered sugar moieties, base modifications, or backbone modifications that increase resistance to nucleolar and extranuclear degradation enzymes, thereby improving dsRNA stability while maintaining therapeutic benefit.
Solution Approach 2:
The patent creates composite structures by combining dsRNA with lipid carriers to form liposome complexes. This composite approach protects dsRNA from degradation through the lipid envelope while enabling efficient cellular delivery, thus improving both stability and therapeutic effectiveness.
3Measurement precision
If specific nucleotide sequences are used in dsRNA, then targeting precision is improved, but manufacturing complexity is worsened
Solution Approach 1:
The patent divides the dsRNA molecule into distinct functional segments: a sense strand and an antisense strand with specific nucleotide sequences. This segmentation allows independent optimization of each strand for targeting precision while simplifying the manufacturing process through modular synthesis approaches.
Solution Approach 2:
The patent introduces specific nucleotide sequences at particular locations within the dsRNA structure to enhance targeting precision for CIDEB mRNA. These local sequence modifications are strategically placed to ensure complementary binding while maintaining overall manufacturing feasibility through standardized synthesis protocols.
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 dsRNA effectively reduces CIDEB expression, providing therapeutic benefits for CIDEB-related diseases and disorders, including NAFLD and NASH, by targeting and suppressing CIDEB gene expression.
Implementation Method 1
The use of double-stranded RNA (dsRNA) to inhibit the expression of CIDEB through RNA interference mechanisms
Data Source
AI summary
Provided are a double-stranded RNA for inhibiting expression of cell-death-inducing DFFA-like effector B (CIDEB) in cells, a cell comprising the double-stranded RNA, and a method of using the dsRNA or the cell to treat diseases or symptoms mediated by or associated with CIDEB expression in a subject.