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Posts Taged protein-engineering

NANBIOSIS U1_Protein Production Platform expands its facilities at the Autonomous University of Barcelona, strengthening its capabilities.

NANBIOSIS Unit 1 Protein Production Platform (PPP) of CIBER-BBN and UAB, has taken a significant step towards enhancing its service capabilities in the field of recombinant protein production and purification.

Until now, due to space constraints at the Institute of Biotechnology and Biomedicine (IBB), U1’s activities were confined to half of a small laboratory. However, thanks to the ongoing commitment of the center to bolster the PPP’s activities, this unit has gained access to a laboratory, along with an office, exclusively designated for the platform within the IBB premises, creating an optimal environment for the process of protein production and purification.

This initiative has not only solidified the space that PPP occupies within the IBB and the UAB but also signifies a boost for UAB’s internal services, reinforcing its position as an integral part of ICTS NANBIOSIS, thereby strengthening its commitment to research and scientific excellence.

The center, in its steadfast support for PPP’s activities, has prioritized the allocation of this new space over other needs, recognizing the potential and strategic importance of this service for advancing molecular research, not only within the institution but also within the scientific community at large.

The immediate impact of this facility expansion has resulted in the provision of an optimal space to accommodate all FPLC-AKTA purification equipment, essential for providing quality service. Additionally, new equipment has been acquired, notably including the incorporation of a large-sized refrigerator capable of housing a FPLC-AKTA unit. This development represents a qualitative leap, enabling the PPP to optimize processes for purifying thermosensitive proteins.

The new spaces of the PPP are now adjacent to the spaces of the Nanobiotechnology Group (NBT), enhancing the exchange of information and knowledge between both, and facilitating direct access to shared resources, thereby stimulating interaction. The combination of expertise in protein design and purification with specialization in nanobiotechnology opens up a broad horizon for innovation and the development of disruptive solutions in various fields.

In the words of the responsible team, “this expansion represents a significant step forward, allowing NANBIOSIS U1 not only to advance in its current service provision but also to open doors to new improvement opportunities”.

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NANBIOSIS U1 PPP invited to PEGS, the Protein & Antibody Engineering Summit

*Image explained by Merce Márquez Martínez, Coordinator of NANBIOSIS U1

The NBT group and Unit 1 of NANBIOSIS (Protein Production Platform, PPP), from CIBER-BBN and IBB-UAB, participated in the 15th PEGS Europe conference held in Lisbon from November 14th to 16th. PEGS, or the Protein & Antibody Engineering Summit, is a prestigious conference, organized by the Cambridge Healthtech Institute (CHI), focusing on protein engineering and its applications in drug discovery, development, and delivery. This conference serves as a valuable platform for knowledge exchange among researchers, scientists, industry experts, and professionals in the field of protein science.

From left to right, Julieta María Sanchez, Merce Márquez, José Luis Corchero and Eloi Parlade

The conference typically includes workshops, seminars, keynote presentations, panel discussions, poster sessions, and exhibitions. These elements allow participants to delve into various aspects of protein engineering, covering topics such as novel technologies, therapeutic targets, biologics development, and innovative strategies for protein design and optimization. PEGS fosters networking, collaboration, and learning in the dynamic field of protein engineering.

The meeting featured parallel sessions covering various thematic areas like engineering, targets, bispecifics, immunotherapy, analytical methods, expression, machine learning, and training seminars. Notably, this year’s focus was on the application of antibodies as treatment platforms, particularly in oncology. Artificial intelligence topic, however, had a significant presence at the conference as a tool for the prediction of protein structures, understanding their functions, and accelerating drug discovery processes. Algorithms were discussed for analyzing extensive biological data to model protein behavior, predict protein folding patterns, identify potential drug targets, and design novel proteins with specific functions. Additionally, tools aiding in protein engineering, optimizing production methods, and facilitating the development of personalized medicine by analyzing individual variations in protein interactions were highlighted.

The NBT group, and PPP from NANBIOSIS, was the only Spanish research group invited to have an active participation in the meeting. Specifically, the group contributed invited oral presentations in the tracks of “cell line and systems engineering”, “Optimizing expression platforms” and “Protein process development”. These oral presentations, along with a poster, focused on presenting the latest results of the group in the field of microparticles as protein-only based platforms for drug delivery and optimizing the production of recombinant proteins in mammalian cells.

In addition, the Technical Coordinator of the NANBIOSIS’s Unit 1 (PPP) was invited as a chairperson to moderate and lead the session titled: “Overcoming expression and production challenges for unique proteins”.

In this setting, connections were established with researchers who share an interest in our work, and there is an anticipation of forging new collaborations.

The upcoming PEGS conference scheduled for 2024 will be held in Barcelona, and the group looks forward to showcasing their latest findings once more.

*Image: Representation by AI of Artificial Microparticles: Robot generating microparticles with embedded DNA fragments.  These particles on micro scale are mainly composed by proteins that self-assemble into these larger structures when cations are added. These particles are able to slowly disintegrate into the constitutive proteins, functioning as an effective platform for drug delivery in several medical applications. Specifically designed as carriers, they provide a sustained and continuous release of protein-based drugs over several days, ensuring controlled and gradual administration for therapeutic purposes.

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Why the poor biodistribution so far reached by tumor-targeted medicines?

Cell-selective targeting is expected to enhance effectiveness and minimize side effects of cytotoxic agents. Functionalization of drugs or drug nanoconjugates with specific cell ligands allows receptor-mediated selective cell delivery. However, it is unclear whether the incorporation of an efficient ligand into a drug vehicle is sufficient to ensure proper biodistribution upon systemic administration, and also at which extent biophysical properties of the vehicle may contribute to the accumulation in target tissues during active targeting. To approach this issue, structural robustness of self-assembling, protein-only nanoparticles targeted to the tumoral marker CXCR4 is compromised by reducing the number of histidine residues (from six to five) in a histidine-based architectonic tag. Thus, the structure of the resulting nanoparticles, but not of building blocks, is weakened. Upon intravenous injection in animal models of human CXCR4+ colorectal cancer, the administered material loses the ability to accumulate in tumor tissue, where it is only transiently found. It instead deposits in kidney and liver. Therefore, precise cell-targeted delivery requires not only the incorporation of a proper ligand that promotes receptor-mediated internalization, but also, unexpectedly, its maintenance of a stable multimeric nanostructure that ensures high ligand exposure and long residence time in tumor tissue.

Protein production has been partially performed by the  ICTS NANBIOSIS U1, Protein Production Platform and the nanoparticle size analysis by the U6  of NANBIOSIS Biomaterial Processing and Nanostructuring Unit. Biodistribution studies were performed by the U18 of the ICTS NANBIOSIS, Nanotoxicology Unit.

The concept presented by the authors of the present research might represent a convincing explanation of the poor biodistribution so far reached by tumor-targeted medicines, including antibody-drug conjugates. In addition to this, they offer a potential developmental roadmap for the improvement of these drugs, of high intrinsic therapeutic potential, to reach satisfactory efficiencies in the clinical context.

Hèctor López-Laguna, Rita Sala, Julieta M. Sánchez, Patricia Álamo, Ugutz Unzueta, Alejandro Sánchez-Chardi, Naroa Serna, Laura Sánchez-García, Eric Voltà-Durán, Ramón Mangues, Antonio Villaverde and Esther Vázquez. Nanostructure Empowers Active Tumor Targeting in Ligand-Based Molecular Delivery. Part. Part. Syst. Charact. 2019.

DOI: 10.1002/ppsc.201900304

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