SCHEMA Computational Design of Virus Capsid Chimeras: Calibrating How Genome Packaging, Protection, and Transduction Correlate with Calculated Structural Disruption

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dc.citation.firstpage724en_US
dc.citation.issueNumber12en_US
dc.citation.journalTitleACS Synthetic Biologyen_US
dc.citation.lastpage733en_US
dc.citation.volumeNumber2en_US
dc.contributor.authorHo, Michelle L.en_US
dc.contributor.authorAdler, Benjamin A.en_US
dc.contributor.authorTorre, Michael L.en_US
dc.contributor.authorSilberg, Jonathan J.en_US
dc.contributor.authorSuh, Junghaeen_US
dc.date.accessioned2017-08-04T12:30:01Zen_US
dc.date.available2017-08-04T12:30:01Zen_US
dc.date.issued2013en_US
dc.description.abstractAdeno-associated virus (AAV) recombination can result in chimeric capsid protein subunits whose ability to assemble into an oligomeric capsid, package a genome, and transduce cells depends on the inheritance of sequence from different AAV parents. To develop quantitative design principles for guiding site-directed recombination of AAV capsids, we have examined how capsid structural perturbations predicted by the SCHEMA algorithm correlate with experimental measurements of disruption in seventeen chimeric capsid proteins. In our small chimera population, created by recombining AAV serotypes 2 and 4, we found that protection of viral genomes and cellular transduction were inversely related to calculated disruption of the capsid structure. Interestingly, however, we did not observe a correlation between genome packaging and calculated structural disruption; a majority of the chimeric capsid proteins formed at least partially assembled capsids and more than half packaged genomes, including those with the highest SCHEMA disruption. These results suggest that the sequence space accessed by recombination of divergent AAV serotypes is rich in capsid chimeras that assemble into 60-mer capsids and package viral genomes. Overall, the SCHEMA algorithm may be useful for delineating quantitative design principles to guide the creation of libraries enriched in genome-protecting virus nanoparticles that can effectively transduce cells. Such improvements to the virus design process may help advance not only gene therapy applications but also other bionanotechnologies dependent upon the development of viruses with new sequences and functions.en_US
dc.identifier.citationHo, Michelle L., Adler, Benjamin A., Torre, Michael L., et al.. "SCHEMA Computational Design of Virus Capsid Chimeras: Calibrating How Genome Packaging, Protection, and Transduction Correlate with Calculated Structural Disruption." <i>ACS Synthetic Biology,</i> 2, no. 12 (2013) American Chemical Society: 724-733. https://doi.org/10.1021/sb400076r.en_US
dc.identifier.digitalSCHEMA_computational_design_virus_capsid_chimerasen_US
dc.identifier.doihttps://doi.org/10.1021/sb400076ren_US
dc.identifier.urihttps://hdl.handle.net/1911/96590en_US
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Chemical Society.en_US
dc.subject.keywordadeno-associated virusen_US
dc.subject.keywordcapsiden_US
dc.subject.keywordchimeraen_US
dc.subject.keywordprotein engineeringen_US
dc.subject.keywordrecombinationen_US
dc.subject.keywordSCHEMAen_US
dc.titleSCHEMA Computational Design of Virus Capsid Chimeras: Calibrating How Genome Packaging, Protection, and Transduction Correlate with Calculated Structural Disruptionen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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