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TitleDesign of bacteriophage T4-based artificial viral vectors for human genome remodeling.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 2928, Year 2023
Publish dateMay 30, 2023
AuthorsJingen Zhu / Himanshu Batra / Neeti Ananthaswamy / Marthandan Mahalingam / Pan Tao / Xiaorong Wu / Wenzheng Guo / Andrei Fokine / Venigalla B Rao /
PubMed AbstractDesigning artificial viral vectors (AVVs) programmed with biomolecules that can enter human cells and carry out molecular repairs will have broad applications. Here, we describe an assembly-line ...Designing artificial viral vectors (AVVs) programmed with biomolecules that can enter human cells and carry out molecular repairs will have broad applications. Here, we describe an assembly-line approach to build AVVs by engineering the well-characterized structural components of bacteriophage T4. Starting with a 120 × 86 nm capsid shell that can accommodate 171-Kbp DNA and thousands of protein copies, various combinations of biomolecules, including DNAs, proteins, RNAs, and ribonucleoproteins, are externally and internally incorporated. The nanoparticles are then coated with cationic lipid to enable efficient entry into human cells. As proof of concept, we assemble a series of AVVs designed to deliver full-length dystrophin gene or perform various molecular operations to remodel human genome, including genome editing, gene recombination, gene replacement, gene expression, and gene silencing. These large capacity, customizable, multiplex, and all-in-one phage-based AVVs represent an additional category of nanomaterial that could potentially transform gene therapies and personalized medicine.
External linksNat Commun / PubMed:37253769 / PubMed Central
MethodsEM (single particle)
Resolution3.9 Å
Structure data

EMDB-40228, PDB-8gmo:
Bacteriophage T4 capsid shell containing 9DE insertions into the gp23* major capsid protein subunits
Method: EM (single particle) / Resolution: 3.9 Å

Source
  • tequatrovirus t4
KeywordsVIRUS LIKE PARTICLE / Bacteriophage T4 / capsid shell / phage display / decorated capsid / phage head

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