Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Generative AAV capsid diversification by latent interpolation Adeno-associated virus (AAV) capsids have shown clinical promise as delivery vectors for gene therapy. However, the high prevalence of pre-existing immunity against natural capsids poses a challenge for widespread treatment. The generation of diverse capsids that are potentially more capable of immune evasion is challenging because introducing multiple mutations often breaks capsid assembly. Here we target a representative, immunologically relevant 28-amino-acid segment of the AAV2 capsid and show that a low-complexity Variational Auto-encoder (VAE) can interpolate in sequence space to produce diverse and novel capsids capable of packaging their own genomes. We first train the VAE on a 564-sample Multiple-Sequence Alignment (MSA) of dependo-parvoviruses, and then further augment this dataset by adding 22,704 samples from a deep mutational exploration (DME) on the target region. In both cases the VAE generated viable variants with many mutations, which we validated experimentally. We propose that this simple approach can be used to optimize and diversify other proteins, as well as other capsid traits of interest for gene delivery.
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The categories of this paper are: toxicology
11
The categories of this paper are: cognition
20
The categories of this paper are: pharmacology
1
The categories of this paper are: bioinformatics
13
The categories of this paper are: animal
4
The categories of this paper are: neuroscience
24
The categories of this paper are: cancer
3
The categories of this paper are: evolutionary
12
The categories of this paper are: behavior
31
The categories of this paper are: paleontology
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The categories of this paper are: epidemiology
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The categories of this paper are: zoology
22
The categories of this paper are: physiology
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The categories of this paper are: pathology
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The categories of this paper are: systems
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The categories of this paper are: developmental