Modified Plant Virus Vectors for Cell-Specific Nucleic Acid Delivery
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Solution Overview
Problem
Current viral delivery systems, such as adenoviral vectors, are limited in their ability to deliver nucleic acids of specific sizes and require re-optimization for different cell types, lacking targeted delivery to specific mammalian cells.
Innovation Solution
Modified plant viruses engineered with specific nucleotide sequences and receptors that allow targeted delivery to mammalian cells expressing the corresponding receptor, enabling transient expression and reducing off-target effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If adenoviral vectors are used for nucleic acid delivery, then delivery capability to various cell types is achieved, but the system requires re-optimization for each new cell type and is limited to specific nucleic acid sizes
Solution Approach 1:
The patent employs a universal plant virus-based delivery platform that can deliver nucleic acids to multiple mammalian cell types without requiring re-optimization for each cell type. The plant virus vector system maintains consistent performance across different cell types, eliminating the need for cell-type-specific vector engineering that plagues adenoviral systems.
Solution Approach 2:
The invention changes the fundamental parameters of the delivery system by transitioning from adenoviral vectors to modified plant viruses. This parameter change includes using plant virus nucleotide sequences, capsid proteins, and entry mechanisms that are inherently compatible with multiple mammalian cell types, thereby resolving the adaptability-complexity contradiction.
2Manufacturing precision
If plant viruses are modified for mammalian cell delivery, then targeted delivery to specific cells is achieved, but the system requires engineering of viral sequences and receptors
Solution Approach 1:
The patent segments the delivery system into two independent components: the plant virus vector carrying the nucleic acid payload, and the receptor system on mammalian cells. This segmentation allows the virus to be engineered once for universal delivery capability, while target specificity is achieved through receptor expression patterns, thereby reducing overall engineering complexity while maintaining high precision.
Solution Approach 2:
The invention introduces a receptor-mediated intermediary mechanism where plant virus particles interact with specifically engineered or naturally occurring receptors on mammalian cells. This intermediary system enables precise targeting without requiring complex re-engineering of the virus for each cell type, as the receptor acts as the specific recognition element.
3Productivity
If conventional viral vectors are used, then nucleic acid delivery is achieved, but off-target effects and immune responses increase
Solution Approach 1:
The patent converts the natural resistance of mammalian cells to plant viruses into a benefit by engineering specific receptor systems that enable controlled entry only into desired cells. This approach eliminates off-target effects because plant viruses naturally do not infect mammalian cells without the specific receptor, turning a previously limiting factor into a safety feature that reduces harmful off-target effects while maintaining delivery efficiency.
Data Source
AI summary
The disclosure provides modified plant viruses designed for delivering a nucleotide of interest into mammalian cells. The modified plant viruses include a plant virus nucleotide sequence (e.g. fragment) that is capable of transfecting a mammalian cell when that mammalian cell expresses a receptor for the modified plant virus. Accordingly, the disclosure also provides receptors for the modified plant viruses as well as methods of using the receptor or the modified plant virus and receptor.