Implantable Device for Sustained Antisense Oligonucleotide Release
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Solution Overview
Problem
Current nucleic acid-based gene therapy delivery methods, particularly those using mRNA, face challenges due to the instability of ribonucleic acids and the difficulty in controllably delivering nucleic acid-encapsulated lipid particles over a sustained period, primarily because the lipids used have a low melting point, making them unsuitable for incorporation into conventional medical devices.
Innovation Solution
An implantable medical device with a core polymer matrix containing ethylene vinyl acetate copolymer, where at least 10% of the internucleoside linkages are chemically modified, allowing for the controlled release of antisense oligonucleotides over a period of about seven days, with a melting temperature and melt flow index optimized to minimize nucleic acid degradation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nucleic acids are encapsulated into lipid particles to protect from degradation and promote cellular uptake, then stability and cellular uptake are improved, but the low melting point of lipids makes it difficult to incorporate them into conventional implantable medical devices
Solution Approach 1:
The patent uses an implantable medical device as an intermediary carrier that delivers the lipid-encapsulated nucleic acid particles to the target site. The device acts as a mediator between the lipid particles and the body, providing controlled release while protecting the temperature-sensitive lipid structure from degradation during storage and transport.
Solution Approach 2:
The patent optimizes physical parameters of the lipid particles, specifically controlling particle size distribution and melting point characteristics, to enable incorporation into implantable devices. By adjusting these parameters, the lipid particles maintain their protective function while becoming compatible with device manufacturing processes.
2Ease of manufacture
If conventional implantable medical devices are used for delivery, then device structure and manufacturing are simplified, but they cannot deliver nucleic acids over a sustained period of time
Solution Approach 1:
The patent transforms the static structure of conventional implantable devices into a dynamic system that enables sustained release. The device incorporates mechanisms such as biodegradable polymers or controllable release matrices that allow gradual degradation or activation over time, enabling nucleic acid delivery to continue for extended periods rather than requiring immediate release.
3Ease of operation
If lipids with low melting point are used to encapsulate nucleic acids, then cellular uptake is promoted, but it becomes difficult to incorporate them into processes and polymer materials used to form implantable medical devices
Solution Approach 1:
The patent applies local quality by creating distinct zones or phases within the implantable device structure. The lipid particles are localized in specific regions of the device where their low melting point properties are advantageous for cellular uptake, while other regions of the device use materials with higher thermal stability for structural integrity and manufacturing compatibility.
Data Source
AI summary
An implantable medical device is provided. The implantable medical device includes a core having an antisense oligonucleotide (ASO) dispersed within a core polymer matrix. The core polymer matrix includes an ethylene vinyl acetate copolymer. The ASO includes one or more nucleosides attached via internucleoside linkages. At least 10% of the internucleoside linkages comprise chemically modified internucleoside linkages. The implantable device is capable of releasing about 5% to about 60% of the ASO after a time period of about seven days.