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 Chopra, Venigalla B. Rao

Research output: Contribution to journalArticle

43 Citations (Scopus)

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

Fingerprint

DNA Packaging
Bacteriophage T4
Capsid Proteins
Head
Plague Vaccine
Active Immunotherapy
Proteins
Viral Genome
Antigen-Presenting Cells
Reporter Genes
Cellular Immunity
Genetic Therapy
Bacteriophages
Nanoparticles
Dendritic Cells
Genes
Vaccines
Adenosine Triphosphate
Ligands
Antibodies

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

In vitro and in vivo delivery of genes and proteins using the bacteriophage T4 DNA packaging machine. / Tao, Pan; Mahalingam, Marthandan; Marasa, Bernard S.; Zhang, Zhihong; Chopra, Ashok; Rao, Venigalla B.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 15, 09.04.2013, p. 5846-5851.

Research output: Contribution to journalArticle

Tao, Pan ; Mahalingam, Marthandan ; Marasa, Bernard S. ; Zhang, Zhihong ; Chopra, Ashok ; Rao, Venigalla B. / In vitro and in vivo delivery of genes and proteins using the bacteriophage T4 DNA packaging machine. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 15. pp. 5846-5851.
@article{aaaa0e1cec2549fe84239c72e1ad6c94,
title = "In vitro and in vivo delivery of genes and proteins using the bacteriophage T4 DNA packaging machine",
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.",
keywords = "Gene therapy, Phage assembly, Protein and dna delivery, Protein display",
author = "Pan Tao and Marthandan Mahalingam and Marasa, {Bernard S.} and Zhihong Zhang and Ashok Chopra and Rao, {Venigalla B.}",
year = "2013",
month = "4",
day = "9",
doi = "10.1073/pnas.1300867110",
language = "English (US)",
volume = "110",
pages = "5846--5851",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "15",

}

TY - JOUR

T1 - In vitro and in vivo delivery of genes and proteins using the bacteriophage T4 DNA packaging machine

AU - Tao, Pan

AU - Mahalingam, Marthandan

AU - Marasa, Bernard S.

AU - Zhang, Zhihong

AU - Chopra, Ashok

AU - Rao, Venigalla B.

PY - 2013/4/9

Y1 - 2013/4/9

N2 - 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.

AB - 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.

KW - Gene therapy

KW - Phage assembly

KW - Protein and dna delivery

KW - Protein display

UR - http://www.scopus.com/inward/record.url?scp=84876065936&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876065936&partnerID=8YFLogxK

U2 - 10.1073/pnas.1300867110

DO - 10.1073/pnas.1300867110

M3 - Article

VL - 110

SP - 5846

EP - 5851

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

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

SN - 0027-8424

IS - 15

ER -