Engineered NK Cells With H84T-BanLec for SARS-CoV-2 Clearance
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Solution Overview
Problem
There is a need for effective treatments and preventive measures against coronaviruses, particularly SARS-CoV-2, as existing therapies are inadequate and patients with severe infections exhibit immune dysregulation, making it difficult to clear the virus, and current treatments lack specificity and stability.
Innovation Solution
Engineering natural killer (NK) cells with a chimeric antigen receptor (CAR) containing a modified banana lectin (H84T-BanLec) domain that specifically targets SARS-CoV-2 envelope glycoproteins, enhancing viral clearance and cytotoxicity while avoiding immunogenicity issues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies are used to treat SARS-CoV-2, then treatment can be provided, but the therapies lack specificity and effectiveness in clearing the virus
Solution Approach 1:
The patent modifies the banana lectin protein by introducing a specific point mutation (H84T substitution) to change its binding parameters. This mutation enhances the lectin's specificity for SARS-CoV-2 envelope glycoproteins while maintaining its ability to bind viral surfaces, thereby improving viral clearance effectiveness without compromising manufacturability
Solution Approach 2:
The engineered banana lectin serves as an intermediary molecule that bridges the immune system and SARS-CoV-2 virus. When administered to patients, the lectin binds to viral envelope glycoproteins and facilitates immune recognition and viral clearance, providing a specific and effective treatment mechanism that overcomes the limitations of existing non-specific therapies
2Reliability
If patients with severe infections are treated, then viral clearance is needed, but immune dysregulation prevents effective clearing
Solution Approach 1:
The engineered banana lectin therapy enables the patient's own immune system to clear the virus by providing a specific binding agent that overcomes immune dysregulation. The lectin self-administers the function of viral recognition and facilitates immune-mediated viral clearance without requiring complex immune modulation protocols
Solution Approach 2:
By introducing the H84T mutation, the lectin's binding parameters are optimized to work effectively even in the presence of immune dysregulation. The modified lectin maintains stable binding to SARS-CoV-2 envelope glycoproteins under varying immune conditions, ensuring reliable viral clearance capability in severe infection scenarios
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 engineered NK cells effectively bind and eliminate SARS-CoV-2, providing a safe and specific treatment option with enhanced antiviral activity, suitable for off-the-shelf use in patients with COVID-19.
Implementation Method 1
a chimeric antigen receptor (CAR) polypeptide comprising an extracellular banana lectin (BanLec) domain... the BanLec domain comprises an amino acid sequence having at least 70, 80, 85, 90, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with an amino acid sequence of SEQ ID NO: 3
Implementation Method 2
enhancing viral clearance and cytotoxicity... The engineered NK cells effectively bind and eliminate SARS-CoV-2
Data Source
AI summary
Provided herein are, inter alia, methods, compositions and kits for treating or preventing coronaviruses, e.g., SARS-CoV-2. Also included herein are kits for treating or preventing coronaviruses, e.g., SARS-CoV-2.