Protease assisted native-protein delivery approach (PANDA)

US10434069B2 · kind B2 · utility

Assignee

• The Regents of the University of California · US

Inventors

• Yi Tang · San Gabriel, US
• Zhen Gu · Los Angeles, US
• Yunfeng Lu · Los Angeles, US
• Ming Yan · Los Angeles, US
• Anuradha Biswas · Los Angeles, US
• Guoping Fan · Dongguan, CN

Key dates

• Filing date: Feb 26, 2016
• Grant date: Oct 8, 2019
• Expiry date: Dec 3, 2037

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K48/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A method for intracellular delivery of single proteins or other cargo molecules by encapsulation within nanocapsules formed by interfacial polymerization of one or more types of monomers and selected protease cleavable cross-linkers is provided. The thin positively charged capsules are readily brought into the cytosol of target cells by endocytosis. The capsules are degraded by the action of endogenous proteases or co-delivered proteases on the cross-linkers releasing the functional cargo unaltered. The cross-linkers can be adapted to be cleavable by specific enzymes selected from available intracellular enzymes within the target cell or co-delivered or self-cleaving when the cargo itself is a protease. The nanocapsules produced by the methods have been shown to have long-term stability, high cell penetration capability, low toxicity and efficient protease-modulated specific degradability without affecting cargo protein function.