Evidence map›Paper›PMID 35985893›Full record

ArticleBiomaterials2022

Multimodal imaging of capsid and cargo reveals differential brain targeting and liver detargeting of systemically-administered AAVs.

Jai Woong Seo, Javier Ajenjo, Bo Wu, Elise Robinson, Marina Nura Raie, James Wang, Spencer K Tumbale, Pablo Buccino, David Alexander Anders, Bin Shen and 9 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Recent developments in translational imaging of in vivo gene therapy outcomes.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Development of [Nuclear medicine and biology
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 1 country.

Jai Woong SeoMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Javier AjenjoMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Bo WuMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Elise RobinsonMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Marina Nura RaieMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
James WangMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Spencer K TumbaleMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Pablo BuccinoStanford Cyclotron & Radiochemistry Facility (CRF), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
David Alexander AndersStanford Cyclotron & Radiochemistry Facility (CRF), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Bin ShenStanford Cyclotron & Radiochemistry Facility (CRF), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Frezghi G HabteStanford Center for Innovation in In vivo Imaging (SCi3), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Corinne BeinatMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Michelle L JamesMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Samantha Taylor ReyesMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Sripriya Ravindra KumarDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Timothy F MilesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Jason T LeeMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Viviana GradinaruDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Katherine W FerraraMolecular Imaging Program at Stanford (MIPS), Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA. Electronic address: kwferrar@stanford.edu.
Stanford University · USCalifornia Institute of Technology · USCenter for Innovation · USStanford Medicine · US

Funding

Specific and high-resolution ultrasound cancer imagingR01CA112356 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI FERRARA, KATHERINE W, FOIRET, JOSQUIN · 2005 to 2022
$6.1M
In vivo PET imaging of novel engineered AAVs informs capsid design in Alzheimer's DiseaseR01EB028646 · NIBIB · STANFORD UNIVERSITY · PI FERRARA, KATHERINE W · 2019 to 2022
$3.8M
NCI NIH HHS R01 CA112356NIBIB NIH HHS R01 EB028646
6 · The paper itself

Abstract

The development of gene delivery vehicles with high organ specificity when administered systemically is a critical goal for gene therapy. We combine optical and positron emission tomography (PET) imaging of 1) reporter genes and 2) capsid tags to assess the temporal and spatial distribution and transduction of adeno-associated viruses (AAVs). AAV9 and two engineered AAV vectors (PHP.eB and CAP-B10) that are noteworthy for maximizing blood-brain barrier transport were compared. CAP-B10 shares a modification in the 588 loop with PHP.eB, but also has a modification in the 455 loop, added with the goal of reducing off-target transduction. PET and optical imaging revealed that the additional modifications retained brain receptor affinity. In the liver, the accumulation of AAV9 and the engineered AAV capsids was similar (∼15% of the injected dose per cc and not significantly different between capsids at 21 h). However, the engineered capsids were primarily internalized by Kupffer cells rather than hepatocytes, and liver transduction was greatly reduced. PET reporter gene imaging after engineered AAV systemic injection provided a non-invasive method to monitor AAV-mediated protein expression over time. Through comparison with capsid tagging, differences between brain localization and transduction were revealed. In summary, AAV capsids bearing imaging tags and reporter gene payloads create a unique and powerful platform to assay the pharmacokinetics, cellular specificity and protein expression kinetics of AAV vectors in vivo, a key enabler for the field of gene therapy.

Indexed as

CapsidDependovirusBrainGenetic VectorsLiverMultimodal ImagingTransduction, Genetic

Identifiers

PMID35985893
PMCPMC9621732
OpenAlexW4290090525

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.