AAV9 vector provides efficient gene transfer in all segments of the renal 
nephron, with minimum expression in non-renal cells, when administered 
retrogradely via the ureter. It is important to restrict the transgene 
expression to the desired cell type within the kidney, so that the physiological 
endpoints represent the function of the transgene expressed in that specific 
cell type within kidney. We hypothesized that segment-specific gene expression 
within the kidney can be accomplished using the highly efficient AAV9 vectors 
carrying the promoters of genes that are expressed exclusively in the desired 
segment of the nephron in combination with administration by retrograde infusion 
into the kidney via the ureter. We constructed AAV vectors carrying eGFP under 
the control of: kidney-specific cadherin (KSPC) gene promoter for expression in 
the entire nephron; Na+/glucose co-transporter (SGLT2) gene promoter for 
expression in the S1 and S2 segments of the proximal tubule; sodium, potassium, 
2 chloride co-transporter (NKCC2) gene promoter for expression in the thick 
ascending limb of Henle's loop (TALH); E-cadherin (ECAD) gene promoter for 
expression in the collecting duct (CD); and cytomegalovirus (CMV) early promoter 
that provides expression in most of the mammalian cells, as control. We tested 
the specificity of the promoter constructs in vitro for cell type-specific 
expression in mouse kidney cells in primary culture, followed by retrograde 
infusion of the AAV vectors via the ureter in the mouse. Our data show that AAV9 
vector, in combination with the segment-specific promoters administered by 
retrograde infusion via the ureter, provides renal nephron segment-specific gene 
expression.