AAV capsid stability
Keeping AAV capsids stable is critical to getting genetic payloads where they need to go – since capsids can break down or aggregate during manufacturing or storage. Even after administration, capsid stability is an important part of making sure your AAV releases its payload exactly when it’s supposed to.
Measuring when an AAV breaks open or aggregates is a problem that usually requires answers from many tools put together, and techniques can be complex, take a long time to run, or require large sample volumes. Functional assays, like transduction or infectivity assays, take days and require highly skilled users, while electron microscopy is low throughput and expensive. Even routine assays like AAV ELISAs, which can be used to measure intact capsid titers, or qPCR, which looks at genome quantification, can take several hours and will only give insight on capsid stability as part of an intricately designed experiment.
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- Capsid stability depends on a lot:
- serotype or recombinant capsid sequence
- packaged genome length
- if genomes are single-stranded or self-complementary
- formulation buffer
- capsid chemical stability, e.g. deamidation
Uncle helps efficiently assess the impact of each of those on stability for an AAV gene therapy vector, and gives insight into the many ways they can impact stability by detecting genome ejection, capsid protein unfolding and aggregation.
The best formulation buffers will be designed to help AAV capsids hold in their genomes as long as possible. From excipients to pH, formulations have a lot going on that can help or hinder capsid stability.
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