Innovative vectorization of biomolecules | InnoVec

Why potent bioactive molecules, in particular the biotechnologically-derived ones that help to improve our knowledge of fundamental mechanisms of the living world, do not easily translate into treatments for human health?

The main issue is related to their poor pharmacodynamic profile and their impediment to access their molecular targets due to cell, tissue and/or environmental barriers. Our institute tackles vectorization issues consisting in the accurate transport of potent and innovative macromolecules (RNAs, proteins) right at their site of action, and dedicates its research to understand and improve timeliness and accuracy in the delivery of the active molecules to fight antibio-resistance and hard-to-treat cancers.

Question 1. How can we fight against the antiobio-resistance of critical pathogenic bacteria?

Bacteria adapt fairly easily to modifications of their environment and find ways to resist to new antibiotic treatments. This fact requires keeping on the discovery of novel substances and tactics for witch the bacteria have not found yet a parade. Discovering novel antibiotic clearly is a challenge. Indeed, the bacterial membrane is a bulwark protecting the bacteria’s life from undesired components including potent drugs. Moreover, many bacteria build biofilms to protect them from external aggressions including chemical ones. The fighting angle of the InnoVec Institute is to favor access of potent antibiotic to their targets by working on the delivery/vectorization issues.

To get there, our teams are developing fundamental research to:

• Understand the mechanisms by which bacteria ensure active entry of nutriments through selected gates within their membranes. The rational is to tentatively divert/hijack these gates for selective transport of innovative components into the bacteria to unravel their potency in a so-called Trojan horse strategy.
• Invent and synthesize new molecules or nanometric devices to favor accumulation of drug payload at the active sites.
• Design and apply microfluidic systems, algorithms, Artifical Intelligence (AI) and biological systems for studying bacteria and their responses to treatments and stimuli.
• Perform a standardized biological evaluation of the various tools developed in the Institute.

Question 2. How can we improve the delivery of therapeutics to cancer cells in their specific microenvironment?

Biotechnology-derived antibodies as well as other classical chemical antitumor substances have considerably improved the treatment of many cancers in patients, resulting in prolonged expectancy and quality of life. However, some patients are left aside as some cancers remain difficult to treat. The true reasons remain elusive but we can point to adaptive physiologic response to treatments and slyness within the healthy cellular environment as important reasons. Moreover, biotechnology-derived compounds and delivery technologies for targeting selected human cells amongst many compartments and cell types still remain at an infancy stage.

The objectives of the InnoVec teams are to work together to:

• Design biomolecules and technologies to specifically target cancer cells. Specifically, we will tackle the issues of delivering nucleic acids and proteins at their site of action though the design of antibody derivatives, viral particles, supramolecular chemical assemblies and electronic/physical methodologies. Targeting components (probes) as well as detection methods will be also developed.
• Understand how some cancer cells respond to treatments and alter their epigenetic and proteomic pattern in a dynamic manner using the help of artificial intelligence (AI) and bio-informatics methodology. This knowledge will be useful for determining the most suitable targets and time window for treatment.
• integrate biosensors in on-chip laboratories or telemetry systems, design mathematical algorithms and AI to observe the mechanisms involved in vectorization
• Develop innovative compounds and tailored delivery systems to target novel signalization pathways relevant to physiological state of cancer cells.
• Develop accurate models of cancers for proof of concept validation and knowledge acquisition.