Minimally invasive endoscopic hydrodynamic gene delivery to target organs

Dr. Kumbhari and his team are developing new ways to safely deliver gene therapy directly into organs such as the liver, pancreas and kidney through endoscopic procedures that endoscopists already perform. A nonviral payload is inserted into the nucleus by leveraging hydrodynamic injection through endoscopic retrograde cholangiopancreatography. In this routine procedure, a flexible camera passes through the mouth into the small intestine to access and treat the bile ducts in the liver.

Using this approach, genetic material is delivered through the liver's natural biliary duct system under carefully controlled pressure. This brief pressure allows genes to enter organ cells efficiently without the need for surgery or viral carriers.

This work demonstrates that genes can be safely delivered, taken up by cells and remain active. Across multiple studies, this method has worked reliably in large animal models, showed no major safety concerns and resulted in long-lasting gene activity in the targeted organs.

This approach is important because it creates a potential pathway for future treatments of liver, pancreatic and kidney diseases using minimally invasive procedures already familiar to clinicians. The end goal is to add helpful genetic instructions directly into organ cells to change disease course and potentially reduce or eliminate the need for lifelong medications in some patients.

Related publications

Kruse RL, Huang Y, Shum T, Bai L, Ding H, Wang ZZ, Selaru FM, Kumbhari V. Endoscopic-mediated, biliary hydrodynamic injection mediating clinically relevant levels of gene delivery in pig liver. Gastrointestinal Endoscopy. 2021.

Kumbhari V, Li L, Piontek K, Ishida M, Fu R, Khalil B, Garrett CM, Liapi E, Kalloo AN, Selaru FM. Successful liver-directed gene delivery by ERCP-guided hydrodynamic injection (with videos). Gastrointestinal Endoscopy. 2018.