Engineered Polypeptide Capsids for Selective Nucleic Acid Delivery
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Solution Overview
Problem
Current methods for selective delivery of nucleic acids and proteins to specific cell types lack specificity and efficiency, hindering targeted therapeutic interventions and cellular communication mechanisms.
Innovation Solution
Engineered non-naturally occurring polypeptides that self-assemble into export compartments, equipped with programmable domains for nucleic acid or protein binding, enable selective packaging and delivery of cargo molecules, such as RNA or proteins, using Gag-homology proteins like Arc or PNMA proteins, which facilitate cell-specific uptake and intercellular transfer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional delivery methods are used, then delivery can be achieved, but specificity and efficiency are insufficient
Solution Approach 1:
The delivery system is segmented into distinct functional domains: an export compartment domain for structural assembly and cellular uptake, and a programmable binding domain for specific cargo recognition. This segmentation allows independent optimization of delivery specificity (through binding domain programming) and efficiency (through export compartment design), resolving the contradiction between precision and productivity.
Solution Approach 2:
The invention employs dynamic, programmable binding domains that can be reconfigured to recognize different cargo molecules. This dynamic adaptability enables the same export compartment structure to achieve high specificity across different delivery targets, maintaining both precision and efficiency without requiring separate delivery systems for each cargo type.
2Measurement precision
If engineered polypeptides with programmable domains are used, then delivery specificity is improved, but device complexity increases
Solution Approach 1:
The export compartment domain serves multiple functions: structural self-assembly, cellular uptake mediation, and cargo protection. The programmable binding domain can be universally applied to recognize different cargo molecules through standard binding motifs. This multi-functionality reduces overall system complexity by eliminating the need for separate specialized components for each function.
Solution Approach 2:
The programmable binding domain is nested within or fused to the export compartment domain, creating a hierarchical structure where the binding domain can be independently programmed while the export compartment provides the structural framework. This nesting allows specific cargo recognition (precision) without requiring complete redesign of the delivery vehicle (complexity reduction).
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 allows for precise delivery of nucleic acids and proteins to target cells, enabling cellular differentiation, biomolecule production, or therapeutic interventions by inducing specific cellular states, including apoptosis or senescence in diseased tissues, with potential applications in adoptive cell therapy and gene editing.
Implementation Method 1
The polypeptide may comprise an export compartment domain that directs self-assembly of the polypeptide into the export compartment
Implementation Method 2
the export compartment domain may be engineered to provide cell-specific uptake of the assembled export compartment
Data Source
AI summary
Provided herein are non-naturally occurring self-assembling polypeptides for transferring nucleic acids and/or proteins to a cell, pharmaceutical compositions comprising such polypeptides, and methods for treatment comprising use of such compositions. The methods for producing polypeptide compositions may include combining in a solution, unassembled recombinant GAG-like proteins, nucleic acids and/or proteins in low salt conditions; and increasing the ionic strength of the solution.