Chimeric Polypeptide for Selective Cancer Cell Targeting
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Solution Overview
Problem
Current cancer therapies often target both cancer and healthy cells, leading to negative health consequences and reduced treatment efficacy due to the difficulty in selectively targeting cancer cells without affecting normal cells.
Innovation Solution
A method involving a chimeric polypeptide with sequence-specific endonuclease and exonuclease activities, guided by a nucleic acid molecule to selectively target and degrade cancer cell-specific nucleic acids, using CRISPR/Cas systems to introduce double-strand breaks and induce exonucleolytic degradation, while minimizing impact on healthy cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer therapies are used to target cancer cells, then cancer cell elimination is achieved, but healthy cells are also damaged leading to negative health consequences
Solution Approach 1:
The patent applies local quality by designing a chimeric polypeptide with distinct functional domains: an endonuclease domain for sequence-specific DNA cleavage at target sites and an exonuclease domain for degradation of cleaved nucleic acids. This localized functional differentiation within the polypeptide structure enables selective cancer cell targeting while sparing healthy cells through precise molecular recognition of cancer-specific nucleic acid sequences.
Solution Approach 2:
The patent uses guide RNA as an intermediary molecule that mediates between the chimeric polypeptide and target DNA. The guide RNA provides sequence-specific recognition of cancer cell nucleic acids, directing the endonuclease and exonuclease activities to only those cells expressing the target sequence, thereby acting as a selective mediator that prevents off-target effects on healthy cells.
2Productivity
If non-specific exonuclease activity is induced to degrade cellular DNA/RNA, then cancer cell death is enhanced, but specificity of targeting is reduced
Solution Approach 1:
The patent applies preliminary action by first using the endonuclease domain to make sequence-specific double-strand breaks in cancer cell DNA guided by cancer-specific sequences. Only after this specific initial cleavage does the exonuclease domain become activated to degrade the nucleic acids. This preliminary sequence-specific action ensures that non-specific exonuclease activity is only induced in cells containing the target cancer-specific sequence, maintaining targeting specificity while enhancing cell death efficiency.
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 the selective elimination of cancer cells by targeting specific nucleic acid sequences unique to cancer cells, reducing harm to healthy cells and enhancing treatment efficacy by ensuring precise cell death mechanisms.
Implementation Method 1
Target nucleic acids are identified through base pairing by a guide nucleic acid molecule
Implementation Method 2
Targeted nucleic acids are cleaved so as to introduce a double-strand break
Implementation Method 3
Target nucleic acid degradation is then facilitated through exonucleolytic activity, such as exonucleolytic activity associated with or fused to the protein component of the nucleoprotein complex
Data Source
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AI summary
Enhanced, specific nucleic acid targeting complexes comprising endo and exonuclease activity, and related methods that allow both targeted degradation of specific and/or non-specific nucleic acids in vivo and specific temporal regulation of nuclease activity to prevent off-target activity are disclosed herein. Through practice of the disclosure, nucleic acids, and cells harboring them, such as cancer cells or pathogens, are selectively degraded in vivo.