Zika Cell-Penetrating Peptide Crosses Blood-Brain Barrier
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Solution Overview
Problem
Current methods for delivering bioactive agents, such as CRISPR/Cas9, face challenges including difficulty penetrating cell membranes, lack of selectivity, and safety concerns due to off-target activity and immune responses, particularly when targeting the brain or other hard-to-reach tissues.
Innovation Solution
Development of a cell-penetrating peptide (CPP) derived from Zika virus, which can cross the blood-brain barrier and deliver therapeutic agents like CRISPR/Cas9 or other effectors into target cells, including neural tissues, by attaching it to a ribonucleoprotein complex or other molecules, allowing for controlled and selective delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If viral vectors are used to deliver gene editing agents, then delivery efficiency is improved, but safety risks increase due to insertional mutagenesis and immune responses
Solution Approach 1:
The patent uses a cell-penetrating peptide (CPP) as an intermediary carrier to deliver CRISPR/Cas9 ribonucleoprotein complexes into cells. The CPP acts as a mediator that enables cellular uptake without using viral vectors, thereby achieving delivery efficiency while avoiding the safety risks associated with viral integration and immune responses. The CPP conjugate system provides a non-viral alternative that maintains therapeutic effectiveness without the harmful side effects of viral delivery methods.
2Adaptability or versatility
If cell membranes are modified to enable penetration of large molecules, then delivery capability is improved, but selectivity is reduced leading to off-target activity
Solution Approach 1:
The patent employs a specifically designed cell-penetrating peptide sequence that provides localized and targeted delivery functionality. The CPP is engineered with specific amino acid characteristics that enable it to penetrate cell membranes while maintaining directionality and specificity for the intended target cells. This localized quality approach ensures that the delivery mechanism operates precisely where needed, avoiding widespread off-target effects that would result from non-specific membrane modification.
3Reliability
If direct injection into organs is used for delivery, then delivery effectiveness is improved, but invasiveness increases
Solution Approach 1:
The patent utilizes a self-service delivery mechanism where the CPP-conjugated CRISPR/Cas9 complex autonomously penetrates cell membranes and delivers its cargo without requiring direct surgical injection into the target organ. The CPP's inherent cell-penetrating properties enable the therapeutic agent to self-administer delivery at the cellular level, achieving effective tissue penetration through systemic administration rather than invasive local injection.
4Productivity
If viral vectors are used for gene delivery, then transduction efficiency is improved, but immune response increases
Solution Approach 1:
The patent converts the potential harm of immune recognition into a benefit by using a non-viral CPP-based delivery system that inherently avoids the immunogenicity of viral vectors. Instead of dealing with the harmful immune responses triggered by viral delivery, the invention uses a synthetic peptide approach that can be designed to minimize immune recognition while maintaining efficient cellular uptake. This transforms the delivery problem from one dominated by immune clearance to one focused on optimizing peptide design for enhanced penetration and reduced immunogenicity.
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
The CPP enables efficient and safe delivery of bioactive agents into specific cells and tissues, reducing off-target effects and immune responses, with the potential for repeated dosing and improved therapeutic outcomes, including gene editing in hard-to-reach organs like the brain.
Implementation Method 1
a cell penetrating peptide (CPP) that crosses the blood brain barrier and delivers Cas9 (or other 'effectors') into target cells
Data Source
AI summary
In various embodiments constructs are provided for the delivery of an effector molecule into a cell. In certain embodiments the construct comprises a cell penetrating peptide (CPP) attached to an effector that is to be delivered into a cell, where the cell penetrating peptide comprises a Zika cell penetrating peptide (Zika CPP), and the effector is selected from the group consisting of a protein, a nucleic acid, an organic compound, a nanoparticle, a viral particle, and the like.