PHARMACEUTICAL BIOTECHNOLOGY: BIOTHERAPEUTIC DRUG DISCOVERY, ENGINEERING, AND DELIVERY

The "Pharmaceutical biotechnology: biotherapeutic drug discovery, engineering, and delivery" course is one of the training activities of the PhD course in Bio and Nanomaterials Science and Technology and is divided in two modules: "Therapeutic peptides and proteins" (module A) and "Therapeutic nucleic acids and living cells" (module B). The module A allows students to acquire the knowledge of the main concepts related to the properties, the development and the applications of the major peptide and protein-based therapeutics. The module B allows students to acquire the knowledge of the main concepts related to the properties, the development and the applications of the major therapies based on nucleic acids and living cells.

The aim of module A ("Therapeutic peptides and proteins") is to introduce the students to the properties and recombinant technologies used to develop and engineer peptide and protein-based therapeutic molecules. The aim of module B ("Therapeutic nucleic acids and living cells") is to introduce the students to the properties and recombinant technologies used to develop therapeutic nucleic acids (e.g., DNA e RNA) and living cell-based therapies (e.g., immune cells, stem cells, red blood cells) currently used in the clinic. Particular attention will be dedicated to the pharmacological, immunological, regulatory, and commercial aspects that must be carefully pondered during the discovery and developmental process of a novel biotherapy. The students are supposed to be able to appreciate the advantages and the disadvantages of the different biotherapeutics and being able to recognise and evaluate, through a critical analysis, which biotherapy may be more suitable for a given disease. At the end of the course, students should be able to i) apply the knowledge acquired, ii) problem solving abilities in new or unfamiliar environments within broader (or multidisciplinary) contexts related to their field of study, iii) have the ability to integrate knowledge and handle complexity, iv) formulate judgements with incomplete or limited information, v) reflect on social and ethical responsibilities linked to the application of their knowledge and judgements, vi) communicate their conclusions, and the knowledge and rationale underpinning these, to specialist and nonspecialist audiences clearly and unambiguously.

Basic knowledge of molecular biology, chemical biology, structural biology, cellular biology, immunology and pharmacology.

Contents of module A (15 hours) include:
• Rudiments of pharmacology and immunology
• Peptide therapeutics: advantages and disadvantages. Natural product derived peptides as starting points for drug discovery. Peptidomimetic and directed evolution technologies in peptide lead discovery. Stapled peptides. Strategies to extend the half-life of peptides.
• Cytokine-based therapies: benefits and limitations. Interleukins approved for therapy. Engineering and synthetic cytokines signalling for therapeutics.
• Non-antibody scaffold drugs: advantages and major challenges. Strategies for the generation of differentiated non-antibody scaffold drugs. Examples of non-antibody scaffold molecules for therapeutic, diagnostic, and biotechnological applications.
• Therapeutic antibodies: properties and mode of actions. Multidimensional engineering of antibodies: antigen binding, Fc receptor binding and modularity. Multispecific antibodies. Antibody fragments. Antibody drug conjugates (ADCs).

Contents of module B (15 hours) include:
• Nucleic acid therapeutics: advantages and disadvantages. Principle of systematic evolution of ligands by exponential enrichment (SELEX). DNA, RNA aptamers. Antisense oligonucleotide (AON). RNA interference (RNAi). Ribozymes. mRNA-based vaccines.
• Mammalian cell-based therapies. Adoptive cell therapy using tumour-infiltrating lymphocytes (TIL). Engineered T cell expressing chimeric antigen receptors (CAR-T). Therapeutic approaches to enhance natural killer (NK) cell cytotoxicity against cancer. Macrophages in immunotherapy. Engineering stem cells for cancer therapy. Dendritic cell (DC) in cancer immunotherapy. Antigen-specific therapeutic approaches for autoimmunity. Therapies based on i) red blood cells and ii) stem cells.
• Engineered bacteria cell-based therapies. Therapies based on i) gut-associated engineered bacteria and ii) tumour-associated engineered bacteria. Bacteriophage therapies.

All needed material will be provided in class.

The assessment of learning takes place by means of a short oral presentation. The objective of the exam consists in verifying and evaluating the ability of the student to include at least one content of the course in her/his current PhD research project. The students must demonstrate both the critical learning of the topics of the entire program and the ability to expose them in a formal and concise manner using an appropriate scientific language. The constant and active participation to the lessons will be taken into account in the final evaluation. Finals will take place within the dates established by the academic calendar.

oral

The evaluation is expressed in thirtieths. The grade is determined by:
• knowledge of the required topics (range 15 points);
• ability to independently articulate the answers (range 5 points);
• confidence in the presentation (range 5 points);
• ability to delve into the topic (range 5 points).
Honors (‘laude’) will be awarded for excellent knowledge and understanding of the program, judgment, and communication skills.

Teaching is organized in frontal theoretical lectures in the classroom. Classroom lectures will be interactive and will include a general introduction to the subject matter by the teacher followed by the presentation of some concrete applications take from scientific articles. Both traditional whiteboard and PowerPoint slides will be used during the lessons. The teaching material is present and downloadable from the University's Moodle e-learning platform.

Accessibility, Disability and Inclusion

Accommodation and support services for students with disabilities and students with specific learning impairments: Ca’ Foscari abides by Italian Law (Law 17/1999; Law 170/2010) regarding support services and accommodation available to students with disabilities. This includes students with mobility, visual, hearing and other disabilities (Law 17/1999), and specific learning impairments (Law 170/2010). In the case of disability or impairment that requires accommodations (i.e., alternate testing, readers, note takers or interpreters) please contact the Disability and Accessibility Offices in Student Services: disabilita@unive.it

This subject deals with topics related to the macro-area "Human capital, health, education" and contributes to the achievement of one or more goals of U. N. Agenda for Sustainable Development