CRISPR Gene Editing to Eliminate JCV Activation Risk
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Solution Overview
Problem
Current immunosuppressive therapies for conditions like multiple sclerosis and autoimmune diseases pose a risk of activating latent John Cunningham Virus (JCV), leading to progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease, due to impaired immune systems, and existing treatments are either ineffective or have significant side effects.
Innovation Solution
Employing gene editing technologies such as CRISPR-associated endonucleases, zinc-finger nucleases, and transcription activator-like effector nucleases to target and eliminate JCV from host cells before or during immunosuppressive therapy, using specific guide RNAs to cleave target sites within the JCV genome, thereby preventing its activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunosuppressive therapy is administered to treat autoimmune diseases and multiple sclerosis, then disease symptoms are improved, but the risk of JCV activation and PML increases
Solution Approach 1:
The patent applies preliminary action by administering gene editing compositions before immunosuppressive therapy to eliminate latent JCV from host cells. The CRISPR-associated endonucleases with guide RNAs are delivered to cleave target sites in the JCV genome prior to starting immunosuppressive treatment, thereby removing the viral threat before it can be activated by immune suppression.
Solution Approach 2:
The patent uses gene editing compositions as an intermediary mechanism between the immunosuppressive therapy and the JCV virus. The CRISPR system acts as a mediator that processes and eliminates the viral genome, allowing immunosuppressive therapy to be administered safely without direct interaction between the therapy and the virus.
2Productivity
If standard immunosuppressive concentrations are used, then therapeutic effect is achieved, but extensive patient monitoring is required due to PML risk
Solution Approach 1:
By performing gene editing to eliminate JCV before therapy initiation, the patent removes the need for extensive monitoring during treatment. The preliminary elimination of the virus allows standard immunosuppressive concentrations to be used without requiring continuous surveillance for PML development.
3Object-affected harmful factors
If immunosuppressive therapy is reduced to sub-optimal concentrations to lower PML risk, then patient safety is improved, but treatment effectiveness decreases
Solution Approach 1:
The patent eliminates the need to reduce immunosuppressive concentrations by performing gene editing beforehand. With JCV removed from host cells through CRISPR-mediated cleavage, patients can receive full therapeutic doses without the PML risk that would otherwise require dose 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 effectively eliminates the risk of JCV activation, allowing for the safe administration of immunosuppressive treatments without the need for sub-optimal concentrations or extensive patient monitoring, potentially making previously risky therapies safer.
Implementation Method 1
administration of compositions including Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated endonucleases, and one or more specific guide RNA sequences, to cleave target sites within the JCV genome
Implementation Method 2
strategies including the administration of JCV-targeting compositions including zinc-finger nucleases (ZFN), or transcription activator-like effector nucleases (TALEN)
Implementation Method 3
strategies including the administration of JCV-targeting compositions including zinc-finger nucleases (ZFN), or transcription activator-like effector nucleases (TALEN)
Data Source
AI summary
A method of eliminating the risk of JCV activation in a subject undergoing immunosuppressive therapy, by administering an effective amount of a gene editing composition directed toward at least one target sequence in the JCV genome, cleaving the target sequence in the JCV genome, disrupting the JCV genome, eliminating the JCV infection, eliminating the risk of JCV activation, and treating the subject with an immunosuppressive therapy. A pharmaceutical composition including at least one isolated nucleic acid sequence encoding a CRISPR-associated endonuclease and at least one gRNA having a spacer sequence complementary to a target sequence in a JCV DNA, the isolated nucleic acid sequences being included in at least one expression vector. Pharmaceutical compositions including at least one isolated nucleic acid sequence encoding at least one TALEN, at least one ZFN, and gene editing composition of C2c1, C2c3, TevCas9, Archaea Cas9, CasY.1-CasY.6, CasX, or argonaute protein, which target at least one nucleotide sequence of the JCV genome.