Mucoadhesive microorganism

US11384123B2 · kind B2 · utility

Assignee

• INTREXON ACTOBIOTICS N.V. · BE

Inventors

• Lothar Steidler · Lokeren, BE
• Klaas Vandenbroucke · Zevergem, BE

Key dates

• Filing date: Sep 21, 2020
• Grant date: Jul 12, 2022
• Expiry date: Jan 9, 2041

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/036
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present disclosure provides genetically modified microorganisms (e.g., bacteria or yeast) with enhanced mucin-binding and/or cell-adhesion properties. For example, the present disclosure provides bacteria exhibiting increased in vitro binding to Caco-2 cells, and increased in vitro binding to mucins. Such microorganisms (e.g., bacteria) can be used, e.g., to deliver bioactive polypeptides to the gastrointestinal tract of a mammalian subject. Modifying the microorganism in the described manner allows for the modulation of gastrointestinal retention and transit times for the microorganism (e.g., bacterium). Exemplary microorganisms (e.g., lactic acid bacteria, such as Lactococcus lactis) contain an exogenous nucleic acid encoding a fusion protein containing a cell-adherence polypeptide, such as CmbA, and a mucin-binding polypeptide, such as a trefoil factor (TFF), e.g., human TFF3. The current disclosure further provides method for making and using the described microorganisms (e.g., bacteria).