Real-time MR tracking of AAV gene therapy with βgal-responsive MR probe in a murine model of GM1-gangliosidosis

Toloo Taghian, Ana Rita Batista, Sarah Kamper, Michael Caldwell, Laura Lilley, Hao Li, Paola Rodriguez, Katerina Mesa, Shaokuan Zheng, Robert M. King, Matthew J. Gounis, Sophia Todeasa, Anne Maguire, Douglas R. Martin, Miguel Sena-Esteves, Thomas J. Meade*, Heather L. Gray-Edwards*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Transformative results of adeno-associated virus (AAV) gene therapy in patients with spinal muscular atrophy and Leber's congenital amaurosis led to approval of the first two AAV products in the United States to treat these diseases. These extraordinary results led to a dramatic increase in the number and type of AAV gene-therapy programs. However, the field lacks non-invasive means to assess levels and duration of therapeutic protein function in patients. Here, we describe a new magnetic resonance imaging (MRI) technology for real-time reporting of gene-therapy products in the living animal in the form of an MRI probe that is activated in the presence of therapeutic protein expression. For the first time, we show reliable tracking of enzyme expression after a now in-human clinical trial AAV gene therapy ( NTC03952637) encoding lysosomal acid beta-galactosidase (βgal) using a self-immolative βgal-responsive MRI probe. MRI enhancement in AAV-treated enzyme-deficient mice (GLB-1−/−) correlates with βgal activity in central nervous system and peripheral organs after intracranial or intravenous AAV gene therapy, respectively. With >1,800 gene therapies in phase I/II clinical trials (, development of a non-invasive method to track gene expression over time in patients is crucial to the future of the gene-therapy field.

Original languageEnglish (US)
Pages (from-to)128-134
Number of pages7
JournalMolecular Therapy Methods and Clinical Development
StatePublished - Dec 10 2021


  • AAV gene therapy
  • GM1 gangliosidosis
  • MR tracking of enzyme expression
  • enzyme-activated contrast agent probes
  • magnetic resonance imaging

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Molecular Biology


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