Plant Cell Bioencapsulated RNAi for Oral Gene Silencing
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Solution Overview
Problem
Current methods for delivering siRNA and other RNA molecules are hindered by inefficient and unsafe delivery systems, with challenges in achieving effective silencing of target genes, particularly for cancer and autoimmune disorders, due to rapid degradation and lack of specific targeting.
Innovation Solution
Development of recombinant plant plastid and viral expression vectors encoding silencing RNA molecules, such as dsRNA, siRNA, and miRNA, which are orally delivered via bioencapsulated plant cells to target specific genes, utilizing chloroplast transformation for high expression levels and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional delivery methods are used for siRNA, then delivery can be achieved, but the delivery system is inefficient and unsafe with rapid degradation
Solution Approach 1:
The patent uses plant cells as intermediary carriers to deliver siRNA to human cells. The plant cell membrane and intracellular structures serve as mediators that protect siRNA from degradation and enable stable delivery. This resolves the contradiction by providing both delivery capability and stability protection through the plant cell intermediary system.
Solution Approach 2:
The patent employs the plant cell membrane as a protective shell that encapsulates and protects siRNA molecules. This flexible membrane structure prevents siRNA degradation while maintaining delivery functionality, thereby improving both reliability and stability simultaneously.
2Reliability
If conventional delivery methods are used for siRNA, then delivery can be achieved, but specific targeting is lacking
Solution Approach 1:
The patent applies local quality by delivering siRNA to specific subcellular locations within human cells (such as the nucleus or specific organelles) rather than throughout the entire cell. This localized delivery enhances both delivery effectiveness and target gene specificity, resolving the contradiction between these two parameters.
3Quantity of substance
If chloroplast transformation is used, then high expression levels are achieved, but the system complexity increases
Solution Approach 1:
The patent utilizes chloroplast transformation systems that can serve multiple functions: producing high levels of dsRNA, providing stable inheritance, and enabling oral delivery. This multi-functionality justifies the increased system complexity by delivering multiple benefits through a single transformation approach, thereby improving quantity of substance while managing complexity through functional integration.
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 effective silencing of target genes, including undruggable oncogenes, with high specificity and stability, offering a cost-effective and easily administered route for treating cancer and autoimmune disorders.
Implementation Method 1
Chloroplast has the exceptional ability to produce abundant transcripts (up to 200,000 copies per ng total RNA)
Implementation Method 2
Delivery of small RNA prepared in more efficient systems as human therapeutics are also severely limited by their methods of delivery... Bioencapsulation within plant cells should protect dsRNA and increase their efficacy
Implementation Method 3
Since the discovery of dsRNA which could silence genes (Fire et al., 1998), RNA interference (RNAi) has been developed as an efficient and powerful tool in plants and animals to silence expression of harmful genes
Data Source
AI summary
Compositions and methods for down-regulating genes through oral administration of RNAi molecule encapsulated in plant cells are provided.