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Next-generation of targeted AAVP vectors for systemic transgene delivery against cancer.

Abstract：

:Bacteriophage (phage) have attractive advantages as delivery systems compared with mammalian viruses, but have been considered poor vectors because they lack evolved strategies to confront and overcome mammalian cell barriers to infective agents. We reasoned that improved efficacy of delivery might be achieved through structural modification of the viral capsid to avoid pre- and postinternalization barriers to mammalian cell transduction. We generated multifunctional hybrid adeno-associated virus/phage (AAVP) particles to enable simultaneous display of targeting ligands on the phage's minor pIII proteins and also degradation-resistance motifs on the very numerous pVIII coat proteins. This genetic strategy of directed evolution bestows a next-generation of AAVP particles that feature resistance to fibrinogen adsorption or neutralizing antibodies and ability to escape endolysosomal degradation. This results in superior gene transfer efficacy in vitro and also in preclinical mouse models of rodent and human solid tumors. Thus, the unique functions of our next-generation AAVP particles enable improved targeted gene delivery to tumor cells.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Suwan K,Yata T,Waramit S,Przystal JM,Stoneham CA,Bentayebi K,Asavarut P,Chongchai A,Pothachareon P,Lee KY,Topanurak S,Smith TL,Gelovani JG,Sidman RL,Pasqualini R,Arap W,Hajitou A

doi

10.1073/pnas.1906653116

subject

Has Abstract

pub_date

2019-09-10 00:00:00

pages

18571-18577

issue

37

eissn

0027-8424

issn

1091-6490

pii

1906653116

journal_volume

116

pub_type

杂志文章

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