Synthetic Virus Genome Design for Expanded Packaging and Infectivity
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Solution Overview
Problem
The packaging capacity of existing viral vectors, such as lentiviruses and adeno-associated viruses, is limited, restricting the amount of heterologous nucleic acid that can be delivered into target cells, and modifying these vectors to include lytic functions while avoiding disruption of essential genes is challenging.
Innovation Solution
A method to produce modified viruses by deleting or inserting heterologous DNA/RNA into specific regions of the viral genome, such as the Deletion Permissive Regions (DPR) between the pin and ipII genes, allowing for the inclusion of additional nucleic acid without disrupting essential virus functions, thereby increasing packaging capacity and infectivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the viral genome is modified to include more heterologous nucleic acid, then the packaging capacity is improved, but the virus production and replication functions are disrupted
Solution Approach 1:
The viral genome is segmented into essential regions (retained) and non-essential regions (deleted/modified). The patent divides the genome structure to identify which parts can be modified without affecting viral function, allowing heterologous nucleic acid insertion in specific permissive regions while preserving critical replication and production genes.
Solution Approach 2:
Non-essential genomic regions are extracted or deleted from the viral genome to create space for heterologous nucleic acid insertion. The patent identifies and removes dispensable DNA sequences from permissive regions, thereby increasing packaging capacity while maintaining essential viral functions through the retained essential regions.
2Adaptability or versatility
If lytic functions are added to the virus for host cell killing, then the therapeutic effect is improved, but the disruption of essential genes increases the risk to virus functionality
Solution Approach 1:
Lytic functions are localized to specific permissive regions of the genome rather than being distributed throughout. The patent inserts lytic gene sequences into defined non-essential regions, ensuring that the killing capability is added locally without interfering with essential viral genes located in protected regions.
Solution Approach 2:
The patent uses permissive regions as intermediary zones that can accommodate additional functions (lytic genes, heterologous nucleic acid) without directly interfering with essential viral functions. These intermediary regions act as buffer zones that mediate between the need for additional functionality and the need to preserve core viral operations.
Data Source
AI summary
The invention relates to modified viruses that are synthetic, compositions comprising such viruses, virus infectivity assays and methods of selecting modified synthetic viruses. The invention also relates to methods of modifying viruses to produce modified synthetic viruses comprising heterologous nucleic acid (DNA or RNA).