Defective Interfering Genes for Broad-Spectrum Viral Prophylaxis
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Solution Overview
Problem
Current antiviral strategies for influenza and coronavirus infections, such as vaccines and neuraminidase inhibitors, have limitations including strain-dependent effectiveness, daily administration requirements, and concerns about drug resistance, highlighting the need for new prophylactic antiviral mechanisms with broad-spectrum effects, especially for individuals with risk factors or severe diseases.
Innovation Solution
Development of defective interfering genes (DIGs) from influenza and coronavirus species, which are designed to inhibit viral infection and replication by delivering nucleic acids encoding these genes using vectors like TAT-P1, forming peptide-polynucleotide nanoparticles, and administering them to provide rapid-onset prophylactic protection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If vaccines are used for viral prevention, then protection is provided, but effectiveness varies from 10-60% and requires at least two weeks to generate sufficient neutralizing antibodies
Solution Approach 1:
The patent introduces defective interfering genes (DIGs) that can provide immediate antiviral protection without requiring the time-consuming immune response generation that vaccines need. The DIGs are delivered directly to cells where they interfere with viral replication from the outset, eliminating the 2-week delay inherent in vaccine-induced antibody production.
2Reliability
If neuraminidase inhibitors are administered daily for prophylaxis, then viral infection is prevented, but drug resistance develops with frequent use
Solution Approach 1:
The patent converts the normally harmful full-length viral genes into beneficial defective interfering genes by introducing deliberate deletions. These DIGs, when delivered to host cells, interfere with viral replication by competing for cellular resources and producing incomplete viral proteins, providing prophylactic protection without the resistance issues associated with conventional antivirals.
3Ease of operation
If conventional antiviral drugs are used, then treatment is provided, but they show benefits only for mild or moderate symptoms and not for severe cases
Solution Approach 1:
The patent creates a universal antiviral approach using defective interfering genes that can protect against multiple virus strains and severities. The DIGs target fundamental viral replication mechanisms rather than specific viral enzymes, providing broad-spectrum protection that works across different disease severities and virus variants.
Data Source
AI summary
The disclosure relates to defective interfering genes and viruses thereof. It has been discovered that defective interfering genes designed from influenza and coronavirus species can inhibit infection or replication of the parent virus. In vivo, DIGs induce rapid-onset prophylactic protection of infected animals against lethal viral doses. Thus, disclosed herein are nucleic acids containing DIGs, pharmaceutical compositions thereof and associated methods of use. For example, described herein is an isolated polynucleotide containing one or more defective interfering genes, wherein each of the one or more defective interfering genes contains a nucleotide sequence corresponding to one or more portions of an influenza or coronavirus gene or genome, wherein the nucleotide sequence includes a deletion in the gene. The DIGs can be in the form of a plasmid. Pharmaceutical compositions of the plasmid can be used to limit viral replication and prevent or treat influenza or coronavirus associated diseases.