Tolerizing Nanoparticles for Gene Therapy Vector Re-Dosing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The immunogenicity of gene therapy vectors and therapeutic proteins expressed from these vectors poses a significant clinical challenge, leading to rapid clearance and immune responses that interfere with re-administration, making periodic re-dosing ineffective and limiting treatment eligibility for patients with pre-existing immunity.
Innovation Solution
The use of negatively charged carrier particles, such as those made of biodegradable polymers like PLGA, encapsulating gene therapy vector antigens or therapeutic proteins, to induce antigen-specific T cell tolerance, thereby reducing immunogenicity and allowing for repeated administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If gene therapy vectors are administered periodically to achieve sustained therapeutic efficacy, then therapeutic benefit is improved, but immunogenicity increases leading to rapid clearance and interference with re-administration
Solution Approach 1:
The patent applies preliminary action by administering tolerizing immune modifying particles (TIMPs) containing vector antigens before re-dosing with the gene therapy vector. This pre-treatment with TIMPs induces antigen-specific tolerance, suppressing the immune response that would otherwise prevent successful re-administration. The TIMPs are given at specific time points (e.g., 1 week, 1 month, or 3 months before re-dosing) to prime the immune system for tolerance, enabling subsequent vector administrations to succeed where they would normally be blocked by immunity.
2Reliability
If immunosuppressive regimens are administered to prevent vector immunogenicity, then re-dosing is enabled, but side effects such as increased infection risk and mortality increase
Solution Approach 1:
The patent applies local quality by using antigen-specific tolerance induction rather than systemic immunosuppression. The TIMPs contain specific vector antigens (such as AAV capsid proteins VP1, VP2, VP3) that target only the immune response against the gene therapy vector. This creates a localized, specific immune modulation effect that spares the rest of the immune system, avoiding the broad immunosuppression side effects (infections, mortality) associated with conventional immunosuppressive drugs. The effect is specific to the vector antigen while leaving other immune functions intact.
3Duration of action of stationary object
If conventional immunosuppressive drugs are used to overcome vector immunogenicity, then therapeutic continuity is improved, but treatment complexity and side effect profile worsen
Solution Approach 1:
The patent applies the taking out principle by extracting and isolating the specific vector antigens from the complete gene therapy vector system. The TIMPs contain only the relevant vector antigens (capsid proteins or other vector components) that trigger the harmful immune response. By separating these specific antigens from the therapeutic vector itself, the invention creates a simplified, targeted approach that eliminates the need for complex combination immunosuppressive regimens. The TIMPs can be administered as simple formulations (e.g., encapsulated antigens in biodegradable particles) given at specific intervals, dramatically simplifying the treatment protocol compared to multiple concurrent immunosuppressive drugs.
Data Source
AI summary
The present application is directed, in general, to tolerizing immune mediated particles comprising gene therapy vector antigens for use in combination with gene therapy regimens in order to reduce immunogenicity to the gene therapy vector antigens and/or transgene protein products expressed by the vectors.