Skin Cell Bioreactor for Systemic Polypeptide Delivery
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Solution Overview
Problem
Current gene therapy methods for delivering nucleic acids to cells face challenges in achieving efficient and sustained delivery of therapeutic agents, particularly due to difficulties in targeting and penetrating specific tissues in vivo, which limits their therapeutic efficacy.
Innovation Solution
The method involves genetically modifying skin cells using engineered viruses, such as adeno-associated viral vectors, to produce and secrete therapeutic polypeptides like antibodies or cytokines systemically, where the skin is pretreated with ultrasound or microdermabrasion to enhance virus penetration and persistence, allowing for non-invasive, long-term production and delivery of biologics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If viruses are delivered by invasive methods to achieve efficient gene transfer, then delivery efficiency is improved, but the complexity and risk of the procedure increases
Solution Approach 1:
The patent uses skin cells as an intermediary platform to produce and deliver therapeutic agents systemically. Instead of directly delivering nucleic acids to target tissues through invasive methods, the invention introduces viral vectors into skin cells, which then function as bioreactors to produce therapeutic proteins that are secreted into the bloodstream, thereby avoiding direct invasive delivery to target organs.
Solution Approach 2:
The skin cells are engineered to autonomously produce and secrete therapeutic agents after receiving the viral vector. The modified skin cells serve themselves as continuous manufacturing plants, eliminating the need for repeated invasive administrations. The cells self-maintain the therapeutic production over extended periods through sustained viral vector expression.
2Productivity
If large doses of virus are administered to overcome delivery barriers, then gene transfer efficiency is improved, but immune response and off-target effects increase
Solution Approach 1:
The patent concentrates the viral vector administration locally in the skin tissue rather than systemically distributing large doses throughout the body. By targeting a specific accessible site (skin), the invention achieves high local concentrations of viral vectors with minimal systemic exposure, thereby reducing off-target effects and immune responses while maintaining efficient gene transfer at the administration site.
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
This approach enables efficient, sustained production and systemic delivery of therapeutic agents, providing immunity or treatment for diseases like HIV, with minimal immune response and off-target effects, utilizing skin cells as an in vivo bioreactor for biologic production.
Implementation Method 1
the skin is pretreated with cavitational ultrasound or microdermabrasion to disrupt the cutaneous stratum corneum
Implementation Method 2
the skin is pretreated with cavitational ultrasound or microdermabrasion to disrupt the cutaneous stratum corneum
Implementation Method 3
administering to the subject an engineered virus comprising one or more foreign nucleic acid sequences encoding one or more target polypeptides, wherein the one or more foreign nucleic acid sequences of the engineered virus are introduced into the target skin cells within the skin
Implementation Method 4
the genetically modified skin cells produce the one or more target polypeptides by expression of the one or more foreign nucleic acid sequences, and wherein the one or more target polypeptides are excreted from the genetically modified skin cells and are introduced systemically within the subject
Data Source
AI summary
A method for the systemic delivery of a polypeptide within a subject is provided by creating genetically modified skin cells via topical introduction of a genetically engineered virus which delivers a nucleic acid encoding a therapeutic polypeptide for expression by the skin cells, wherein the expressed therapeutic polypeptide is secreted by the skin cells and is introduced into the circulatory system of the subject.