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Positron emission tomography imaging of novel AAV capsids maps rapid brain accumulation.
Seo, Jai Woong; Ingham, Elizabeth S; Mahakian, Lisa; Tumbale, Spencer; Wu, Bo; Aghevlian, Sadaf; Shams, Shahin; Baikoghli, Mo; Jain, Poorva; Ding, Xiaozhe; Goeden, Nick; Dobreva, Tatyana; Flytzanis, Nicholas C; Chavez, Michael; Singhal, Kratika; Leib, Ryan; James, Michelle L; Segal, David J; Cheng, R Holland; Silva, Eduardo A; Gradinaru, Viviana; Ferrara, Katherine W.
Afiliação
  • Seo JW; Molecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Ingham ES; Department of Biomedical Engineering, University of California, Davis, CA, USA.
  • Mahakian L; Department of Biomedical Engineering, University of California, Davis, CA, USA.
  • Tumbale S; Department of Biomedical Engineering, University of California, Davis, CA, USA.
  • Wu B; Molecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Aghevlian S; Molecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Shams S; Molecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Baikoghli M; Department of Biomedical Engineering, University of California, Davis, CA, USA.
  • Jain P; Department of Molecular and Cellular Biology, University of California, Davis, CA, USA.
  • Ding X; Molecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Goeden N; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Dobreva T; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Flytzanis NC; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Chavez M; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Singhal K; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Leib R; Stanford University Mass Spectrometry, Stanford, CA, USA.
  • James ML; Stanford University Mass Spectrometry, Stanford, CA, USA.
  • Segal DJ; Molecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
  • Cheng RH; Genome Center and Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, USA.
  • Silva EA; Department of Molecular and Cellular Biology, University of California, Davis, CA, USA.
  • Gradinaru V; Department of Biomedical Engineering, University of California, Davis, CA, USA.
  • Ferrara KW; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Nat Commun ; 11(1): 2102, 2020 04 30.
Article em En | MEDLINE | ID: mdl-32355221
ABSTRACT
Adeno-associated viruses (AAVs) are typically single-stranded deoxyribonucleic acid (ssDNA) encapsulated within 25-nm protein capsids. Recently, tissue-specific AAV capsids (e.g. PHP.eB) have been shown to enhance brain delivery in rodents via the LY6A receptor on brain endothelial cells. Here, we create a non-invasive positron emission tomography (PET) methodology to track viruses. To provide the sensitivity required to track AAVs injected at picomolar levels, a unique multichelator construct labeled with a positron emitter (Cu-64, t1/2 = 12.7 h) is coupled to the viral capsid. We find that brain accumulation of the PHP.eB capsid 1) exceeds that reported in any previous PET study of brain uptake of targeted therapies and 2) is correlated with optical reporter gene transduction of the brain. The PHP.eB capsid brain endothelial receptor affinity is nearly 20-fold greater than that of AAV9. The results suggest that novel PET imaging techniques can be applied to inform and optimize capsid design.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encéfalo / Dependovirus / Tomografia por Emissão de Pósitrons Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encéfalo / Dependovirus / Tomografia por Emissão de Pósitrons Idioma: En Ano de publicação: 2020 Tipo de documento: Article