LTR Retroelements for Targeted Cargo Vesicle Delivery
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Solution Overview
Problem
Current delivery systems for therapeutics face challenges such as large particle sizes and inconsistency, leading to off-target effects and inefficiency in delivering cargos to target cells.
Innovation Solution
Engineered delivery vesicles utilizing endogenous LTR retroelement polypeptides, such as PNMA proteins, with packaging elements and cargos, optionally including fusogenic and targeting moieties, are developed to create smaller, consistent vesicles for targeted cellular delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If viruses and virus-like particles are used to deliver therapeutics to target cells, then delivery capability is achieved, but particle size becomes large and generation consistency becomes difficult
Solution Approach 1:
The patent extracts and utilizes only the essential packaging function from viruses by employing endogenous LTR retroelement polypeptides (such as PNMA proteins) that can package cargo without requiring the complete viral structure. This extraction approach maintains delivery capability while eliminating the need for large viral particles and complex viral assembly processes.
Solution Approach 2:
The patent creates simplified copies of viral packaging functions using endogenous retroelement proteins that replicate the cargo-packaging capability of viruses but with a much simpler structure. These retroelement-based packaging systems produce smaller, more consistent particles that maintain the essential delivery function without the bulk and variability of full viral particles.
2Reliability
If viruses and virus-like particles are used to deliver therapeutics to target cells, then delivery capability is achieved, but generation consistency becomes poor
Solution Approach 1:
The patent employs endogenous LTR retroelement polypeptides that are naturally expressed within host cells, allowing the cell's own machinery to produce the packaging proteins and assemble cargo-loaded particles. This self-service approach eliminates the need for external viral vector production systems, resulting in more consistent and reproducible particle generation with better manufacturing precision.
3Quantity of substance
If larger virus-like particles are used for delivery, then cargo capacity is increased, but off-target effects increase
Solution Approach 1:
The patent applies local quality by using endogenous retroelement proteins that are naturally expressed in specific cell types, creating a localized delivery system. The packaging elements and cargo interaction occur in a controlled manner within the host cell, ensuring that delivery is targeted to the intended cell type and reducing off-target effects while maintaining adequate cargo capacity through optimized packaging element-cargo interactions.
Data Source
AI summary
Provided herein are compositions, systems, and methods for delivering cargo to a target cell. The compositions, systems, and methods comprise one or more polynucleotides encoding one or more LTR retroelement polypeptides for forming a delivery vesicle and one or more capture moieties for packaging a cargo within the delivery vesicle. The one or more LTR retroelement polypeptides for forming a delivery vesicle may comprise two or more of an LTR retroelement gag protein, a retroelement envelope protein, an LTR retroelement reverse transcriptase, or a combination thereof. The LTR retroelement polypeptide alone, the LTR retroelement envelope protein alone, or both the LTR retroelement-derived polypeptide and LTR retroelement envelope protein may be endogenous. In some embodiments the LTR-retroelement-derived polypeptide is a PNMA polypeptide.