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Design of bacteriophage T4-based artificial viral vectors for human genome remodeling.
Zhu, Jingen; Batra, Himanshu; Ananthaswamy, Neeti; Mahalingam, Marthandan; Tao, Pan; Wu, Xiaorong; Guo, Wenzheng; Fokine, Andrei; Rao, Venigalla B.
Afiliación
  • Zhu J; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC, 20064, USA.
  • Batra H; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC, 20064, USA.
  • Ananthaswamy N; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC, 20064, USA.
  • Mahalingam M; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC, 20064, USA.
  • Tao P; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC, 20064, USA.
  • Wu X; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC, 20064, USA.
  • Guo W; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC, 20064, USA.
  • Fokine A; Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA.
  • Rao VB; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC, 20064, USA. rao@cua.edu.
Nat Commun ; 14(1): 2928, 2023 05 30.
Article en En | MEDLINE | ID: mdl-37253769
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Genoma Humano / Bacteriófago T4 Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Genoma Humano / Bacteriófago T4 Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
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