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Hydrodynamic Renal Pelvis Injection for Non-viral Expression of Proteins in the Kidney
Published on: January 8, 2018
Molecular Survival Strategies Against Kidney Filtration: Implications for Therapeutic Protein Engineering
William P Heaps1, Anne Elise Packard1, Kristina M McCammon1
1Department of Physics and Astronomy, Brigham Young University, Provo, UT 84602, USA.
None:
The glomerular filtration barrier poses a significant challenge for circulating proteins, with molecules below ~60-70 kDa facing rapid renal clearance. Endogenous proteins have evolved sophisticated evasion mechanisms including oligomerization, carrier binding, electrostatic repulsion, and FcRn-mediated recycling. Understanding these natural strategies provides blueprints for engineering therapeutic proteins with improved pharmacokinetics. This review examines how endogenous proteins resist filtration, evaluates their application in protein engineering, and discusses clinical translation including established technologies (PEGylation, Fc-fusion) and emerging strategies (albumin-binding domains, glycoengineering). We address critical challenges of balancing half-life extension with tissue penetration, biological activity, and immunogenicity-essential considerations for the rational design of next-generation therapeutics with optimized dosing and enhanced efficacy.
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