Viral Library Generation via Segmented Recombination
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Solution Overview
Problem
Current methods for generating viruses with diverse properties for applications like oncolytic therapy face challenges in achieving sufficient diversity and specificity, particularly in promoting inter-serotype and inter-species recombination, which limits the development of effective oncolytic viruses and other therapeutic agents.
Innovation Solution
A process involving two culturing steps: first, culturing viruses of different serotypes from the same species to promote intra-species recombination, followed by culturing the recombined viruses with those from a different species to enhance inter-species recombination, with optional mutagenesis to further diversify the viral library.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If multiple viral serotypes from different species are pooled together for recombination, then viral diversity increases, but recombination efficiency between different species decreases
Solution Approach 1:
The patent segments the viral pool generation into two distinct phases: first generating intra-species recombinants separately within each species, then combining these enriched pools to generate inter-species recombinants. This segmentation ensures high recombination efficiency at each stage while achieving overall viral diversity across species boundaries.
Solution Approach 2:
The patent performs preliminary intra-species recombination events before combining different species pools. By pre-enriching each species pool with diverse intra-species recombinants, the preliminary action creates a foundation that facilitates more effective inter-species recombination when pools are combined, thereby improving overall recombination efficiency while maintaining viral diversity.
2Manufacturing precision
If incremental genome modifications are used to generate viruses with desired properties, then virus specificity is improved, but the time and resources required to generate diverse viral libraries increase
Solution Approach 1:
The patent employs self-service by allowing viruses to undergo random recombination events naturally when co-cultured, rather than requiring directed incremental modifications. This self-driven recombination process generates diverse viral libraries much faster than methodical genome editing while still producing viruses with desired properties through subsequent selection.
Solution Approach 2:
The patent changes the approach from modifying individual viral genomes incrementally to changing the population-level parameters by pooling multiple serotypes and allowing statistical recombination. This parameter shift enables parallel generation of numerous viral variants simultaneously, dramatically reducing development time while maintaining the ability to select for specific properties.
3Device complexity
If only a limited number of adenovirus serotypes are used for oncolytic therapy, then development complexity is reduced, but the therapeutic effectiveness against resistant tumors is limited
Solution Approach 1:
The patent creates a universal viral library that incorporates multiple adenovirus species (A-G), each with different cellular tropisms and biological properties. This multi-functional pool can target diverse tumor types and mechanisms of resistance, providing universal applicability across different cancer indications while maintaining manageable development complexity through standardized pool generation methods.
Solution Approach 2:
The patent generates composite viral libraries by combining recombinant viruses from multiple species pools. These composite libraries contain chimeric viruses with mixed genomic elements from different species, creating a diverse arsenal that can overcome various resistance mechanisms. The composite approach maintains complexity control by using systematic pool combination strategies rather than individual virus development.
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
This approach maximizes viral library diversity, enabling the creation of new viruses with enhanced properties for oncolytic therapy, vaccines, and gene therapy vectors by increasing the chances of recombination events across the viral genome, thereby expanding the therapeutic potential of adenoviruses and other double-stranded DNA viruses.
Implementation Method 1
culturing together, on one or more cell lines, viruses of at least two different serotypes from a first species of double-stranded DNA virus
Implementation Method 2
combining (i) viruses obtained from Step (a), with (ii) viruses of at least two different serotypes of the same species from each of one or more further species of double-stranded DNA viruses
Data Source
AI summary
This invention relates to a process for producing a library of viruses, comprising first and second culturing steps. These steps aim to promote intra-species and inter-species recombination, respectively, between double-stranded DNA viruses of the same virus family.