Critical aspects of viral vectors for gene transfer into the kidney

Viral vectors have been used in vitro and in vivo for more than a decade, w ith some significant results in specific situations, e.g., when recombinant adeno-associated virus is used for the long-term transduction of skeletal muscle in coagulation factor IX-deficient patients. However, the kidney has been quite difficult to transduce with any viral vector currently availabl e. When viral transduction occurs, it is often heterogeneous, transient, an d eventually associated with immune and toxic side effects. However, recomb inant adeno-associated virus and lentiviral vectors remain to be fully eval uated in the kidney; the former is small enough to be filtered through the glomerular basement membrane. This may be critical, because glomerular filt ration is required for DNA complex-mediated transduction of tubular cells. An alternative to in situ renal gene transfer is secretion of a therapeutic protein from a distant site, such as skeletal muscle. Several examples pro vide evidence that this could be a clinically relevant approach. It also ma y allow accurate determination of the pathophysiologic mechanisms involved in the establishment and maintenance of experimental glomerulonephritis.