Therapeutic Interfering Particles for Variant-Resistant SARS-CoV-2 Suppression
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Solution Overview
Problem
Existing treatments and vaccines for SARS-CoV-2 infections are inadequate against new variants and mutant strains, necessitating the development of therapies that can interfere with infection and facilitate recovery.
Innovation Solution
Recombinant SARS-CoV-2 constructs, known as therapeutic interfering particles (TIPs), which include specific regions of the SARS-CoV-2 genome and packaging signals, replicate in the presence of SARS-CoV-2, competing for viral replication machinery and inhibiting its replication up to 100-fold.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing vaccines and treatments are used, then current strain infections can be addressed, but new variants and mutant strains continue to develop and remain resistant
Solution Approach 1:
The patent segments the SARS-CoV-2 genome into specific functional regions (5' UTR, 3' UTR, packaging signals) and recombines them into defective particles that cannot replicate independently. This segmentation allows the therapeutic particles to interfere with viral replication without requiring the full viral genome, thereby maintaining effectiveness against new variants while avoiding the limitation of existing vaccines.
Solution Approach 2:
The patent creates copies of specific SARS-CoV-2 genomic regions (5' UTR, 3' UTR, packaging signals) to form therapeutic interfering particles. These copies are designed to be non-replicating defective particles that compete with the wild-type virus for cellular resources, effectively interfering with viral replication across various strains including new variants.
2Productivity
If therapeutic interfering particles are designed to replicate in the presence of SARS-CoV-2, then interference with viral replication is enhanced, but the particles must be engineered to be non-replicating by themselves
Solution Approach 1:
The patent divides the SARS-CoV-2 genome into discrete functional segments (5' UTR, 3' UTR, packaging signals) and assembles them into defective particles. This segmentation enables the particles to replicate conditionally in the presence of wild-type virus while preventing independent replication, achieving high interference productivity with manageable engineering complexity.
Solution Approach 2:
The patent modifies the replication parameters of the therapeutic particles by deleting essential coding regions while retaining regulatory elements. This parameter change enables the particles to replicate conditionally (only in the presence of SARS-CoV-2) rather than independently, enhancing their interference capability while controlling their replication behavior through precise genomic manipulation.
3Reliability
If the intervening sequence is made longer to ensure non-replication, then the particle cannot replicate by itself, but the total length increases the complexity of the construct
Solution Approach 1:
The patent segments the genome into essential (5' UTR, 3' UTR, packaging signals) and non-essential (coding regions) parts. By deleting only the coding regions while retaining the regulatory segments, the patent achieves reliable non-replication with minimal increase in construct complexity, avoiding the need for excessively long intervening sequences.
Solution Approach 2:
The patent extracts and removes the coding regions from the SARS-CoV-2 genome to create the therapeutic interfering particles. This extraction of functional coding sequences while preserving regulatory elements achieves non-replication capability without requiring unnecessarily long intervening sequences, thereby reducing overall construct complexity.
Data Source
AI summary
Described herein are compositions of recombinant SARS-CoV-2 constructs and particles that can interfere with or block infection of uninfected cells. The compositions and methods described herein are useful for treatment of SARS-Co V-2 infections. The recombinant SARS-CoV-2 construct cannot replicate by itself, but can replicate in the presence of infective SARS-CoV-2 (e.g., replication competent SARS-CoV-2). Thus, the present application in one aspect provides a recombinant SARS-Co V-2 construct (e.g., SARS-CoV-2 TIP) capable of interfering with SARS-CoV-2 replication, wherein the recombinant SARS-CoV-2 construct cannot replicate by itself, and wherein the recombinant SARS-CoV-2 construct can replicate in the presence of SARS-CoV-2.