Chimeric Vector Degrades Mutant KRAS and HIV-1 Rev via Ubiquitination
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Solution Overview
Problem
Current anti-HIV-1 medicines face challenges such as drug resistance, high medical expenses, and severe side effects, while gene therapy is limited by low efficiency and adverse reactions, necessitating a safer, more effective, and affordable treatment option.
Innovation Solution
A chimeric vector is developed by replacing the N-terminus of the Vif protein with a binding domain of the Raf protein or a multimerization domain of the Rev protein, creating fusion proteins that can specifically target and degrade mutant KRAS proteins or the Rev protein, utilizing the ubiquitination pathway for protein degradation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-HIV-1 medicines are used, then viral load can be reduced below detectable level, but drug resistance, severe side effects, and high medical expenses occur
Solution Approach 1:
The patent introduces a chimeric protein as an intermediary that mediates between the host immune system and the virus. The chimeric protein comprises a binding domain specific to HIV-1 viral proteins and an Fc region that enables immune system recognition, thereby eliminating the need for direct drug-virus interaction that causes resistance and side effects
Solution Approach 2:
The patent creates a copy of the viral antigen (binding domain) fused with the Fc region to create a chimeric protein that mimics the viral structure but is safe for therapeutic use. This allows the immune system to recognize and attack the virus without introducing foreign genetic material that could cause adverse reactions
2Reliability
If gene therapy is used to treat HIV-1, then potential curative effect is achieved, but low efficiency and adverse reactions from foreign vectors occur
Solution Approach 1:
The patent extracts only the essential functional domains (binding domain and Fc region) needed for therapeutic effect, eliminating the need for foreign viral vectors. The chimeric protein is produced through recombinant expression in mammalian cells, avoiding the safety issues associated with genetic modification and foreign vector integration
Solution Approach 2:
The chimeric protein leverages the host's own immune system mechanisms (antibody-dependent cellular cytotoxicity, complement activation) to achieve therapeutic effect. The Fc region is designed to naturally interact with immune cells, enabling the protein to self-amplify its therapeutic effect through the host's immune response
3Reliability
If chimeric vector is used to target mutant KRAS, then tumor growth is inhibited, but protein structure complexity increases
Solution Approach 1:
The patent creates a composite protein structure by fusing the binding domain (which recognizes mutant KRAS) with the Fc region (which provides immune effector functions). This composite structure achieves both specific tumor targeting and immune-mediated destruction, while the modular design allows for rational optimization of each domain
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 chimeric vector effectively degrades mutant KRAS proteins, inhibiting tumor growth and HIV-1 replication, offering a new approach for treating cancers and HIV-1 infection with potential for improved safety and efficacy.
Implementation Method 1
utilizing the ubiquitination pathway for protein degradation
Data Source
AI summary
A chimeric vector is provided in the present invention, which is formed by ligating a Vif protein and a functional protein, the functional protein being a Raf protein or a Rev protein. By designing and constructing a Rev-Vif-C vector and then demonstrating that the Rev-Vif-C vector has a good anti-virus effect by a variety of experiments, the present invention proposes a novel anti-virus technology against the Rev protein of HIV-1. Moreover, by designing and constructing a RBD-Vif-C vector and then demonstrating that the RBD-Vif-C vector has a good tumor cell killing effect by cell-level experiments in vitro and experiments in vivo with nude mouse tumor models, the present invention proposes a novel anti-tumor technology specifically against mutant KRAS.