In vitro and in vivo delivery of genes and proteins using the bacteriophage T4 DNA packaging machine

Pan Tao, Marthandan Mahalingam, Bernard S. Marasa, Zhihong Zhang, Ashok K. Chopra, Venigalla B. Rao

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

The bacteriophage T4 DNA packaging machine consists of a molecular motor assembled at the portal vertex of an icosahedral head. The ATP-powered motor packages the 56-μm-long, 170-kb viral genome into 120 nm × 86 nm head to near crystalline density. We engineered this machine to deliver genes and proteins into mammalian cells. DNA molecules were translocated into emptied phage head and its outer surface was decorated with proteins fused to outer capsid proteins, highly antigenic outer capsid protein (Hoc) and small outer capsid protein (Soc). T4 nanoparticles carrying reporter genes, vaccine candidates, functional enzymes, and targeting ligands were efficiently delivered into cells or targeted to antigen-presenting dendritic cells, and the delivered genes were abundantly expressed in vitro and in vivo. Mice delivered with a single dose of F1-V plague vaccine containing both gene and protein in the T4 head elicited robust antibody and cellular immune responses. This "pro-gene delivery" approach might lead to new types of vaccines and genetic therapies.

Original languageEnglish (US)
Pages (from-to)5846-5851
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number15
DOIs
StatePublished - Apr 9 2013

Keywords

  • Gene therapy
  • Phage assembly
  • Protein and dna delivery
  • Protein display

ASJC Scopus subject areas

  • General

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