Viral Vector Transduction Using mTOR and Restriction Factor Inhibitors
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Solution Overview
Problem
Existing methods for transducing cells using viral vectors face challenges due to the inhibitory effects of mammalian target of rapamycin (mTOR) and antiviral restriction factors, which hinder efficient delivery of exogenous agents.
Innovation Solution
Administering an inhibitor of mTOR and/or antiviral restriction factors, such as SAMHD1, IFITM1, or IFITM3 inhibitors, alongside a viral vector with a fusogen embedded in the lipid bilayer, to enhance transduction efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a viral vector is used to deliver an exogenous agent to cells, then gene therapy can be achieved, but transduction efficiency is hindered by mTOR and antiviral restriction factors
Solution Approach 1:
The patent applies preliminary action by administering mTOR inhibitors and antiviral restriction factor inhibitors before viral vector administration. This pre-treatment approach suppresses the harmful inhibitory effects in advance, creating a more favorable environment for subsequent viral transduction and improving overall transduction efficiency
Solution Approach 2:
The patent uses mTOR inhibitors and antiviral restriction factor inhibitors as intermediary substances that mediate between the viral vector and the cellular environment. These intermediaries modify the cellular state to reduce resistance against viral transduction, enabling more efficient gene delivery without directly altering the viral vector itself
2Productivity
If inhibitors of mTOR and antiviral restriction factors are administered to improve transduction efficiency, then delivery of exogenous agents is enhanced, but treatment complexity increases
Solution Approach 1:
The patent merges multiple therapeutic components into a single integrated treatment protocol. By combining mTOR inhibitors, antiviral restriction factor inhibitors, and viral vectors in a coordinated administration regimen, the treatment achieves enhanced delivery efficiency while managing complexity through systematic integration rather than separate sequential treatments
Data Source
AI summary
Provided herein are methods of transducing or delivering an exogenous agent to a cell using a viral vector pseudotyped with a paramyxovirus and an inhibitor of the mammalian target of rapamycin (mTOR). In some embodiments, the methods can further include the administration of an antiviral restriction factor inhibitor and/or a cytokine.


