Development of imaging reporter genes for mapping adeno-associated viral gene therapy targeted to kidney cells

Tammy Louise Kalber (primary)
Department of Imaging, Division of Medicine
University College London
Prof David Long (secondary)
Department of Developmental Biology and Cancer
UCL GOS Institute of Child Health

Abstract

Adeno-associated viruses (AAV) have shown great promise for gene therapy. However, there is a lack of data determining their distribution and persistence in target tissues. To overcome this, we will develop imageable reporter genes to track AVV expression using in vivo imaging. Our reporter genes will be linked to an AAV targeted to kidney cells, previously shown to affect the function and vascularization of abnormal kidney’s. We will deliver AVV via an ultrasound guided intrarenal artery injection and use photoacoustic imaging to create 3 dimensional maps of AAV gene expression alongside longitudinal changes in vascularisation and function of the kidney.


References

Jathoul A, et al. Nature Photonics 2015;9:239–246 – “Deep in vivo photoacoustic imaging of mammalian tissues using a tyrosinase-based genetic reporter”

Huang J.L. et al. JASN 2016:27(1):69 – “Vascular Endothelial Growth Factor Therapy for the Kidney: Are We There Yet?”

Scarfe L et al. Sci Rep 2015;5:13601 – 2Measures of kidney function by minimally invasive techniques correlate with histological glomerular damage in SCID mice with adriamycin-induced nephropathy”

Zaw-Thin M et al. Sci Rep 2020;10(1):7514 – “Stem cell delivery to kidney via minimally invasive ultrasound-guided renal artery injection in mice”

Stowe C et al. PLoS One. 2015;10(11):e0140730. – “Flow-Based Single Cell Deposition for High-Throughput Screening of Protein Libraries”


BBSRC Area
Molecules, cells and industrial biotechnology
Area of Biology
GeneticsPhysiology
Techniques & Approaches
EngineeringGeneticsImage ProcessingMolecular Biology