Multispecific Molecule for Lung Mucosal SARS-CoV-2 Delivery
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Solution Overview
Problem
Current treatments for COVID-19, particularly targeting SARS-CoV-2, lack effective therapeutic options and struggle with delivering antibodies to the lung mucosa where infection occurs, leading to inadequate containment and treatment of the virus.
Innovation Solution
Development of multispecific molecules comprising a binding domain that targets the polymeric immunoglobulin receptor (pIgR) for systemic administration to the lung mucosa, combined with a second binding domain that specifically binds to SARS-CoV-2, such as the spike glycoprotein, to neutralize the virus.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibody treatments are administered systemically, then the antibodies can be delivered to the lung mucosa, but the delivery efficiency is insufficient and the therapeutic effect is inadequate
Solution Approach 1:
The therapy is divided into two functional segments: a first binding domain that targets pIgR for mucosal delivery and a second binding domain that targets SARS-CoV-2 for viral neutralization. This segmentation allows each domain to be optimized for its specific function, improving both delivery efficiency and therapeutic effect.
Solution Approach 2:
The multispecific molecule combines multiple functions in a single therapeutic agent: it serves as both a delivery vehicle (via pIgR binding) and a viral neutralizing agent (via SARS-CoV-2 binding). This multi-functionality resolves the contradiction by integrating delivery and therapeutic effects into one system.
2Reliability
If monoclonal antibodies are used to target SARS-CoV-2, then the virus can be neutralized, but the delivery to the lung mucosa remains insufficient
Solution Approach 1:
The pIgR binding domain acts as an intermediary that facilitates transport across the mucosal barrier. By first binding to pIgR on the mucosal surface, the molecule gains access to the lung mucosa where SARS-CoV-2 infection occurs, thereby improving delivery while maintaining viral neutralization capability.
Solution Approach 2:
The therapy transitions from a single-function approach to a multidimensional approach by incorporating both mucosal targeting (pIgR binding) and viral targeting (SARS-CoV-2 binding) capabilities. This dimensional expansion allows simultaneous achievement of effective delivery and viral neutralization.
3Ease of manufacture
If existing therapeutic options are used, then treatment can be administered, but the containment of viral infection is inadequate
Solution Approach 1:
The therapeutic molecule is constructed as a composite structure combining a pIgR binding domain and a SARS-CoV-2 binding domain. This composite design enables the molecule to simultaneously interact with both the mucosal barrier and the virus, thereby improving viral containment while maintaining ease of administration.
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 multispecific molecules efficiently transcytose across the lung epithelium, effectively binding and neutralizing SARS-CoV-2, providing a promising avenue for treating COVID-19 by targeting the virus at the site of infection.
Implementation Method 1
The multispecific molecules efficiently transcytose across the lung epithelium
Implementation Method 2
the second binding domain that specifically binds to SARS-CoV-2, such as the spike glycoprotein, to neutralize the virus
Data Source
AI summary
Provided herein are multispecific molecules comprising a first binding domain that specifically binds to polymeric immunoglobulin receptor (pIgR) and a second binding domain that specifically binds to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related methods for the treatment of patients infected with SARS-CoV-2.