Binary Nucleic Acid Construct for HPV Immune Response
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Solution Overview
Problem
Current methods for inducing an immune response against human papillomavirus (HPV) infections are inadequate in effectively combating HPV, particularly types 6, 11, 16, and 18, which cause significant clinical issues including cervical cancer, as existing therapies fail to elicit a robust and sustained immune response.
Innovation Solution
A binary nucleic acid construct system is developed, comprising a first synthetic coding sequence encoding a fusion protein of HPV E6 and E7 amino acid sequences with codon replacements that enhance immune response, and a second construct encoding a ubiquitin molecule to increase intracellular proteolytic degradation, delivered via expression vectors without signal or targeting sequences, to promote immune activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional HPV vaccination or therapy methods are used, then some immune response is achieved, but the response is not robust or sustained enough to effectively combat HPV infections
Solution Approach 1:
The patent divides the immune response induction into two separate nucleic acid constructs: one encoding the HPV E6-E7 fusion protein and another encoding the ubiquitin-proteasome system components. This segmentation allows each construct to be optimized independently for its specific function, with the first construct focused on antigen presentation and the second on enhancing proteolytic degradation, thereby achieving a more robust and sustained immune response compared to conventional single-construct approaches
Solution Approach 2:
The patent creates a composite therapeutic system by combining two distinct nucleic acid constructs with different functions into a unified treatment regimen. The first construct contains the synthetic E6-E7 fusion protein coding sequence, while the second construct contains ubiquitin and proteasome subunit sequences. This composite approach synergistically enhances both antigen presentation and intracellular degradation pathways, producing a more reliable and sustained immune response against HPV infections
2Stability of the object's composition
If wild-type HPV coding sequences are used, then the natural protein structure is maintained, but the immune response is insufficient compared to codon-optimized sequences
Solution Approach 1:
The patent applies codon optimization to the HPV E6 and E7 coding sequences, systematically replacing codons to enhance translation efficiency and immune recognition while preserving the amino acid sequence. This parameter change at the nucleic acid level (without altering the protein structure) significantly boosts the immune response, as the optimized codons facilitate better protein expression and presentation to the immune system
3Ease of operation
If signal sequences are included in expression vectors, then protein targeting and localization are improved, but the complexity of the vector system increases
Solution Approach 1:
The patent deliberately excludes signal sequences and targeting elements from the expression vectors used to deliver the nucleic acid constructs. This extraction of unnecessary components simplifies the vector design and reduces complexity, while the therapeutic effect is achieved through intracellular expression and the natural cellular machinery for protein processing and presentation, eliminating the need for complex external targeting signals
Data Source
AI summary
Disclosed are therapeutic compositions and methods for inducing an immune response to human papillomavirus (HPV). More particularly, disclosed is a method for inducing an immune response in a subject by introducing and expressing a nucleic acid molecule encoding an immunogenic HPV antigen.