Intervening in disease through genetically-modified bacteria

Author(s)

Ferreira, Adilson K. ^{[1, 2]} ; Mambelli, Lisley I. ^[2] ; Pillai, Saravanan Y. ^[3]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Tumor Immunol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Alchemy Innovat Res & Dev, CIETEC IPEN, Sao Paulo - Brazil

^[3] Epiexpressions, Rotterdam - Netherlands

• Document type: Journal article
• Source: BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY; v. 31, n. 6, p. 693-697, DEC 2017.
• Web of Science Citations: 2

Abstract

The comprehension of the molecular basis of different diseases is rapidly being dissected as a consequence of advancing technology. Consequently, proteins with potential therapeutic usefulness, including cytokines and signaling molecules have been identified in the last decades. However, their clinical use is hampered by disadvantageous functional and economic considerations. One of the most important of these considerations is targeted topical delivery and also the synthesis of such proteins, which for intravenous use requires rigorous purification whereas proteins often do not withstand digestive degradation and thus cannot be applied per os. Recently, the idea of using genetically modified bacteria has emerged as an attempt to evade these important barriers. Using such bacteria can deliver therapeutic proteins or other molecules at place of disease, especially when disease is at a mucosal surface. Further, whereas intravenously applied therapeutic proteins require expensive methodology in order to become endotoxin-free, this is not necessary for local application of therapeutic proteins in the intestine. In addition, once created further propagation of genetically modified bacteria is both cheap and requires relatively little in conditioning with respect to transport of the medication, making such organisms also suitable for combating disease in developing countries with poor infrastructure. Although first human trials with such bacteria were already performed more as a decade ago, the recent revolution in our understanding of the role of human gut microbiome in health and diseases has unleashed a revolution in this field resulting in a plethora of potential novel prophylactic and therapeutic intervention against disease onset and development employing such organisms. Today, the engineering of human microbiome for health benefits and related applications now chances many aspects of biology, nanotechnology and chemistry. Here, we review genetically modified bacteria methodology as possible carriers of drug delivering and provided the origin and inspirations for new drug delivery systems. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 15/18528-7 - Development of new drug candidate for the treatment of non-small cell lung cancer: CHY-1 as a novel inhibitor of autophagy and prototype of a novel class of inhibitors of the enzyme CTP: phosphoethanolamine citidililtransferase
• Grantee: Adilson Kleber Ferreira
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 13/07273-2 - Rational design and development of new prototypes derived of antitumor phospholipids as potential inhibitors of the enzyme CtP: phosphoethanolamine citidililtransferase and antitumor agents in non-small cell lung cancer
• Grantee: Jose Alexandre Marzagão Barbuto
• Support type: Regular Research Grants