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Microsphere-adenoviral complexes target and transduce the glomerulus in vivo
N S Nahman1, T J Sferra, J Kronenberger
1Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA. nahman-1@medctr.osu.edu
Kidney International
|September 30, 2000
Summary
Adenoviral-microsphere complexes effectively deliver DNA to glomeruli in rats, a promising gene therapy tool for kidney diseases like glomerulonephritis.
Area of Science:
- Nephrology
- Gene Therapy
- Biotechnology
Background:
- Glomerulonephritis necessitates novel therapeutic strategies targeting glomerular cells.
- Gene therapy offers a potential avenue for treating glomerular diseases.
- Adenoviruses and microspheres are established tools for gene transfer and particle delivery, respectively.
Purpose of the Study:
- To investigate the efficacy of adenoviral-microsphere complexes for in vivo gene transfer into glomerular cells.
- To determine if this complex can achieve DNA transfer (transduction) into kidney glomeruli.
Main Methods:
- Replication-deficient adenoviruses carrying luciferase or beta-galactosidase transgenes were complexed with polystyrene microspheres (11 or 16 micrometers).
- Rats received aortic injections of these adenoviral-microsphere complexes.
- Glomerular transduction and transgene expression were assessed 48 hours and 21 days post-injection.
Main Results:
- Adenoviral-microsphere complexes successfully transduced up to 19% of glomeruli per kidney section.
- Both endothelial and mesangial cells within the glomeruli were transduced.
- Transgene expression persisted for 21 days, with higher efficiency observed using 16 micrometer microspheres.
Conclusions:
- Aortic injection of adenoviral-microsphere complexes is an effective method for in vivo glomerular transduction.
- This approach represents a potential tool for developing gene therapies for glomerular diseases.