Abstract:
:Lentiviral vectors pseudotyped with the baculovirus envelope protein GP64 transduce primary cultures of human airway epithelia (HAE) at their apical surface. Our goal in this study was to harness a directed evolution approach to develop a novel envelope glycoprotein with increased transduction properties for HAE. Using error-prone PCR, a library of GP64 mutants was generated and used to prepare a diverse pool of lentiviral virions pseudotyped with GP64 variants. The library was serially passaged on HAE and three GP64 mutations were recovered. Single-, double- and the triple-combination mutant envelope glycoproteins were compared with wild-type GP64 for their ability to transduce HAE. Our results suggest that lentiviral vectors pseudotyped with evolved GP64 transduced HAE with greater efficiency than wild-type GP64. This effect was not observed in primary cultures of porcine airway epithelial cells, suggesting that the directed evolution protocol was species specific. In summary, our studies indicate that serial passage of a GP64 mutant library yielded specific variants with improved HAE cell tropism, yielding tools with the potential to improve the success of gene therapy for airway diseases.
journal_name
Gene Therjournal_title
Gene therapyauthors
Sinn PL,Hwang BY,Li N,Ortiz JLS,Shirazi E,Parekh KR,Cooney AL,Schaffer DV,McCray PB Jrdoi
10.1038/gt.2017.78subject
Has Abstractpub_date
2017-10-01 00:00:00pages
674-679issue
10eissn
0969-7128issn
1476-5462pii
gt201778journal_volume
24pub_type
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