Liver-Specific RNA for Targeted Anti-Fibrotic Protein Expression
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Solution Overview
Problem
Current therapeutic agents for liver diseases, particularly liver fibrosis and cirrhosis, are inadequate, with existing treatments like TRAIL showing systemic toxicity and short half-life, and no effective targeted anti-fibrotic therapies available.
Innovation Solution
Development of an RNA encoding specific peptides or proteins such as extracellular matrix proteases, CEBPA, TRAIL, HNF4A, FGF21, OGFRL1, HGF, Relaxin 1, 2, and 3, or their variants, for use in treating or preventing liver diseases by enhancing protein expression in liver tissue.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If systemic administration of TRAIL or collagenase is used to treat liver fibrosis, then anti-fibrotic effect is achieved, but systemic toxicity occurs
Solution Approach 1:
The patent uses liver-specific promoters (such as albumin promoter, AAT promoter, or AFP promoter) to drive expression of anti-fibrotic proteins specifically in liver cells. This ensures that the therapeutic effect is localized to the liver tissue where fibrosis occurs, while minimizing exposure and toxic effects in other organs and tissues of the body.
Solution Approach 2:
The patent employs RNA molecules (such as mRNA or siRNA) as intermediaries to deliver therapeutic genes to liver cells. These RNA molecules serve as mediators that enable localized protein expression within the liver without requiring systemic administration of active drugs, thereby reducing systemic toxicity while maintaining therapeutic efficacy.
2Reliability
If recombinant TRAIL is administered to achieve anti-fibrotic effect, then protein activity is obtained, but half-life is short requiring large and frequent dosing
Solution Approach 1:
The patent introduces genetic material (DNA or RNA) into liver cells that encodes anti-fibrotic proteins. This preliminary genetic intervention enables the cells to produce the therapeutic proteins continuously over an extended period, eliminating the need for repeated administrations and providing sustained therapeutic effect.
Solution Approach 2:
The patent enables liver cells to self-produce anti-fibrotic proteins by introducing expression-capsable genetic material. Once the genetic material is taken up by the cells, they autonomously transcribe and translate the therapeutic proteins, providing continuous self-service production without requiring external replenishment through frequent dosing.
Data Source
AI summary
The present invention relates to an RNA suitable for treatment or prophylaxis of liver diseases. In particular, the present invention provides an RNA encoding at least one peptide or protein selected from the group consisting of an extracellular matrix protease, CCAAT/enhancer-binding protein alpha (CEBPA), TNF-related apoptosis-inducing ligand (TRAIL), Hepatocyte Growth Factor (HGF), hepatocyte nuclear factor 4 alpha (HNF4A), fibroblast growth factor 21 (FGF21), opioid growth factor receptor-like 1 (OGFRL1), Relaxin 1 (RLN1), Relaxin 2 (RLN2) and Relaxin 3 (RLN3), or a fragment or a variant of any of these peptides or proteins. The present invention concerns said RNA as well as compositions and kits comprising the RNA. Furthermore, the present invention relates to the RNA, compositions or kits as disclosed herein for use as a medicament, in particular for treatment or prophylaxis of a liver disease. The present invention also provides the use of the RNA, compositions or kits as disclosed herein for increasing the expression of said encoded protein, in particular in gene therapy.