Developing predictive in vitro Glomerulus , Proximal Tubule and Loop of Henle renal cell model platforms to investigate the renal uptake and nephrotoxic liability of large molecules

Biologics represent a new modality of drug molecules which is rapidly expanding in market share. Several studies have demonstrated the biodistribution of siRNA and antisense oligonucleotide (ASO) is highly weighted to the kidney. Targeted uptake of siRNA and ASO by has been exploited as a mechanism to deliver specific siRNA and ASO to silence genes in the kidney. However, the non-specific nature of the interaction between large molecules and specific segments of the renal tubule has also generated off target nephrotoxicity. To better understand the interaction of large molecules (ASOs, siRNA, ADCs large peptides) with different segments of the tubule, we have developed novel primary cell culture models of the glomerulus /podocytes (GPCs) proximal tubule (PTC) and Loop of Henle (LOH) platforms to investigate both the mechanisms of large molecule interactions along the nephron.