Antisense IL-10 Adjuvant Composition for Stronger Vaccine Response
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Solution Overview
Problem
Existing vaccines and therapeutics struggle to effectively enhance immune responses against infections and diseases due to the inhibitory effects of IL-10, which suppresses immune activation and clearance of infected cells.
Innovation Solution
Development of antisense inhibitor adjuvant compositions comprising nucleotide sequences complementary to IL-10 or IL-10RA genes, utilizing modified nucleotides with 2′-O-methyl, 2′-O-ethyl, or 2′-methoxyethyl substituents, morpholino subunits, and phosphorous-containing linkages, designed to sterically block RNA function and enhance immune response by suppressing IL-10 activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If IL-10 is used to regulate immunity and reduce inflammation, then immune suppression and inhibition of immune responses occur, but effective immune response enhancement against infections becomes difficult
Solution Approach 1:
The patent extracts and targets the specific harmful component (IL-10) responsible for immune suppression. By using antisense oligonucleotides that specifically bind to IL-10 mRNA, the invention selectively removes or blocks the function of this single immunosuppressive factor without affecting other immune regulatory mechanisms, thereby resolving the contradiction between maintaining immune regulation and achieving effective immune response.
Solution Approach 2:
The invention converts the harmful immunosuppressive effect of IL-10 into a benefit by using IL-10 itself as a target for antisense therapy. The measured and controlled suppression of IL-10 through antisense oligonucleotides transforms the previously harmful immune inhibition into a controlled therapeutic effect that enhances vaccine efficacy and immune response against infections.
2Manufacturing precision
If antisense oligonucleotides are designed to bind to IL-10 mRNA splice acceptor region, then exon 4 skipping and reduced IL-10 translation occur, but achieving sufficient immune response enhancement requires optimized binding characteristics
Solution Approach 1:
The patent systematically optimizes key parameters of the antisense oligonucleotides including sequence composition, length, modified nucleotide ratios, and binding affinity (ΔG values). By adjusting these parameters, the invention achieves optimal balance between specific binding to IL-10 mRNA (ensuring sequence specificity) and sufficient immune response enhancement, resolving the contradiction between precision and efficacy.
3Stability of the object's composition
If modified nucleotides with 2′-O-methyl, 2′-O-ethyl, or 2′-methoxyethyl substituents are used, then nuclease resistance and stability improve, but molecular complexity and synthesis difficulty increase
Solution Approach 1:
The patent applies modified nucleotides selectively at specific positions within the antisense oligonucleotide sequence rather than uniformly throughout. This local modification strategy provides sufficient nuclease resistance and stability at critical binding regions while minimizing overall molecular complexity and synthesis difficulty, thereby resolving the contradiction between stability and complexity.
4Reliability
If a single mismatch ('blebmer') is introduced to enhance steric blocking, then RNA function blocking is improved, but hybridization stability may be reduced
Solution Approach 1:
The patent strategically places a single mismatch (blebmer) at a specific position within the antisense oligonucleotide sequence to pre-establish enhanced steric blocking capability. This preliminary design feature ensures that when the oligonucleotide binds to IL-10 mRNA, the mismatch creates immediate physical obstruction that prevents ribosomal binding and translation initiation, while the overall hybridization stability is maintained through optimized surrounding sequence composition and modified nucleotides.
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 antisense inhibitor adjuvants enhance immune responses by reducing IL-10 levels, thereby improving the efficacy of vaccines and therapeutics against a wide range of infectious diseases and pathogen infections, including SARS-COV-2, Ebola, and other viral, bacterial, and parasitic diseases.
Implementation Method 1
a free energy (ΔG) of hybridization of −25 to −35 kcal/mol
Implementation Method 2
uniform modifications of each nucleotide with 2′-O-methyl, 2′-O-ethyl, or 2′-methoxyethyl substituents
Implementation Method 3
uniform replacement of the ribose sugar with a morpholino subunit and phosphorous-containing intersubunit linkages, (PMO), dimethylamine-linked phosphate, or methylphosphonate
Data Source
AI summary
Described herein are antisense inhibitor adjuvant compositions comprising modified nucleotide sequences complementary to a Homo sapiens interleukin 10 (IL-10) or interleukin 10 receptor alpha (IL-10RA) genes and methods for use thereof.