CRISPR Cancer Therapy Using Guide RNA for Specific Cell Targeting
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Solution Overview
Problem
Current anticancer therapies often cause significant side effects due to their non-specificity in targeting cancer cells, leading to the killing of both cancer and normal cells, highlighting the need for a treatment that can selectively target cancer cells based on their unique DNA sequence differences.
Innovation Solution
A pharmaceutical composition comprising a polynucleotide that complements specific nucleic acids in cancer cells, combined with a nuclease, such as a CRISPR-associated protein, to selectively kill cancer cells by targeting single nucleotide polymorphisms or copy number variations unique to cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapy or radiotherapy is used to kill cancer cells, then cancer cell proliferation is controlled, but normal proliferating cells are also damaged causing serious side effects
Solution Approach 1:
The patent applies local quality by designing a therapy that delivers different treatments to different cells based on their genetic characteristics. The CRISPR-Cas9 system with patient-specific gRNAs enables localized genetic editing only in cancer cells that harbor specific mutations, while leaving normal cells unaffected. This spatial and cellular specificity resolves the contradiction between effective cancer cell killing and protection of normal cells.
Solution Approach 2:
The patent segments the cancer cell population based on their unique genetic mutations. By identifying and targeting specific mutations present only in cancer cells (and not in normal cells), the therapy divides the treatment approach into cell-type-specific interventions. This segmentation allows selective targeting of cancer cells while sparing normal proliferating cells from damage.
2Reliability
If targeted therapeutic agents are used to control specific cancer cell pathways, then cancer progression is inhibited, but the interaction strength is not specific enough leading to adverse side effects
Solution Approach 1:
The patent applies parameter changes by shifting from protein-level targeting to DNA sequence-level targeting. By using CRISPR-Cas9 to directly edit the genetic code and correct specific mutations, the therapy achieves higher specificity at the molecular parameter level. This fundamental change in the target parameter (from proteins to DNA sequences) enables precise intervention in cancer cell pathways without the cross-reactivity issues that cause adverse side effects.
Solution Approach 2:
The patent replaces the mechanical/chemical binding mechanism of antibody-drug conjugates with a programmable molecular recognition system. The guide RNA in the CRISPR-Cas9 system provides sequence-specific recognition of mutant DNA through complementary base pairing, replacing the less specific protein-protein or protein-drug interactions. This substitution of the targeting mechanism achieves higher specificity and reduces adverse side effects.
3Reliability
If biomarker proteins are used as targets for immunotherapeutic agents, then cancer cells can be recognized, but the interaction is not specific enough to avoid affecting normal cells
Solution Approach 1:
The patent introduces an intermediary molecular recognition system between the therapeutic agent and the target. The guide RNA acts as an intermediary that specifically recognizes and binds to mutant DNA sequences through complementary base pairing, mediating the delivery of the Cas9 enzyme to the precise genomic location. This intermediary mechanism provides higher specificity compared to direct antibody-biomarker interactions, enabling cancer cell recognition without affecting normal cells.
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 highly specific targeting and killing of cancer cells, minimizing harm to normal cells, thereby offering a safer and more effective treatment option by leveraging CRISPR technology to induce apoptosis in cancer cells.
Implementation Method 1
a polynucleotide complementarily binding to a nucleic acid specifically present in cancer cells
Implementation Method 2
a nuclease, such as a CRISPR-associated protein, to selectively kill cancer cells
Data Source
AI summary
A pharmaceutical composition for treating cancer, containing a crRNA and an endonuclease as active ingredients is disclosed. The composition can be customized according to the needs of patients or cell types by specifically treating cancer cells on the basis of specific binding properties of DNA and RNA. The nuclease activity of a CRISPR PLUS system, containing both an endonuclease and an exonuclease can be activated by means of the binding between crRNA and a gene specifically found in cancer cells. Therefore, the cancer treatment effect of the composition is more specific than that of other anti-cancer agents that have been developed up till now.