A prokaryotic-eukaryotic hybrid viral vector for delivery of large cargos of genes and proteins into human cells.
Animals
Antigens
/ immunology
Bacteriophage T4
/ genetics
Cell Line
Dependovirus
/ genetics
Endosomes
/ metabolism
Eukaryota
/ metabolism
Eukaryotic Cells
/ metabolism
Gene Transfer Techniques
Genetic Engineering
Genetic Vectors
/ genetics
Humans
Mice
Nanoparticles
/ chemistry
Transduction, Genetic
Transgenes
Vaccines, DNA
/ immunology
Viruses
/ genetics
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
13
02
2019
accepted:
11
07
2019
entrez:
29
8
2019
pubmed:
29
8
2019
medline:
8
5
2020
Statut:
epublish
Résumé
Development of safe and efficient nanoscale vehicles that can deliver large molecular cargos into human cells could transform future human therapies and personalized medicine. Here, we design a hybrid viral vector composed of a prokaryotic virus (bacteriophage T4) and a eukaryotic virus [adeno-associated virus (AAV)]. The small 25-nm AAV is attached to the large 120 nm × 86 nm T4 head through avidin-biotin cross-bridges using the phage decoration proteins Soc and Hoc. AAV "piggy-backed" on T4 capsid, by virtue of its natural ability to enter human cells acted as an efficient "driver," delivering the largest payloads of foreign DNA (up to 170 kb) and protein (up to 1025 molecules) reported to date, and elicited robust immune responses in mice against flu and plague pathogens and conferred complete protection against lethal pneumonic plague challenge. The T4-AAV represents a unique platform for assembly of natural building blocks into potential therapeutics against genetic and infectious diseases.
Identifiants
pubmed: 31457098
doi: 10.1126/sciadv.aax0064
pii: aax0064
pmc: PMC6703872
doi:
Substances chimiques
Antigens
0
Vaccines, DNA
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaax0064Subventions
Organisme : NIAID NIH HHS
ID : R01 AI064389
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI056443
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI111538
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI082086
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI060549
Pays : United States
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