STUDENT: FEDERICO BRUNELLO (Global committed Listeners)

Week 1

<aside> 🎨 Student: Federico Brunello - Pharmatech Academy Graduate Student - University of Naples, Italy

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Q1: Describe a biological engineering application or tool you want to develop and why

As a M. Sc. graduate in “Cellular and Molecular Biotechnology” (cancer biology track) with a post-masters qualification in “GMP Compliance Quality Expert for Pharmaceutical Operations”, currently enrolled at a post-masters specialization course in RNA pharmaceuticals and Gene Therapy at the University of Naples, Italy, I am particularly interested in the applications of synthetic biology to drug discovery and development of mRNA vaccines and biologicals (ADC antibodies). I am very interested in learning more about the potential impact of AI and synthetic biology to accelerate pipeline for the de-novo design of biopharmaceuticals and in the implementation of synthetic biology to the design of new, personalized cancer biotherapeutics. Finally, I would like to learn more about the potential of synthetic biology-engineered bacteria to actively target specific tumours in the human body (line of research currently being explored at Columbia University) and would like to explore how novel de-novo synthesized genetic circuits and functions might be embedded onto a bacterial chassis running on a minimum genome to produce advanced biopharmaceuticals for a more effective and personalized therapeutic approach to cancer research.

After interning at a US multinational in Synthetic Biology R&D in summer 2012, I completed my B.sc. degree in Italy with a dissertation in the field of Synthetic Biology. During my M. Sc. course, I took additional modules in Startup Lab and Synthetic Biology, where I received initial lab training with iGem biobricks, and graduated with a M.sc. dissertation in the area of Microbial Fuel Cells, blending aspects of electrotechnology and biotechnology. Subsequently, I kept working on Microbial Fuel Cells in the UK with a six months postgraduate internship and then worked for a year as a Research Technician in Synthetic Biology at the University of Exeter. I then specialized with a postmasters qualification in “GMP Compliance Quality Expert for Pharmaceutical Operations” and interned for six months in mRNA vaccines QC at a major CDMO company in Italy.

At the moment, I am undertaking a post-masters specialization course in gene therapy and RNA-based pharmaceuticals at the University of Naples, Italy.

The opportunity to work at the development of synthetic-biology engineered bacteria for cancer therapy or at the synthetic biology-enhanced development of personalized mRNA vaccines against cancer could constitute a great opportunity to advance the fight against tumors with powerful and personalized treatment options.

At the moment, I am seeking opportuinties to undertake work at a Synthetic Biology company or to undertake a PhD starting Fall 2025.

Q2: describe one or more governance/policy goals related to ensuring that this application or tool contributes to an "ethical" future, like ensuring non-malfeasance (preventing harm).

The advancements in AI utilization in drug discovery and development pipelines, the expansion of curated databases of genes and sequences from a variety of organisms, together with the expansion of direct digital-to-gene gene synthesis technologies (e.g. Cambrian Genomics), as well as the expansion and encouragement of synthetic biology startups and grassroot open wet-lab organizations, besides constituting a fantastic achievement that may accelerate innovation fields as diverse as biofuels, renewable energy, alternative materials, and drug discovery and development, poses as well several potential questions about the ethical use of synthetic biology and in the management of potential accidental or wanted malfeasance issues.

In my opinion, potential malfeasance issues of synthetic biology shall be addressed in a dual way, both via education of the synthetic biology and the wider biologists community to the correct and ethical use of this technology as well as with an agreed, mutually negotiated international legal framework addressing the need to prevent and block any unauthorized or malicious users to access, print or embed malicious DNA sequences that might encode or be used to manufacture dangerous biotechnology-derived products.

For what regards anti-cancer mRNA vaccines and synthetic biology-based enhanced ADCs targeting cancer cells, stringent quality control checks will need to be performed to make sure synthetic mRNA molecules and ADCs do not have any hazardous or off-target effects. Synthetic mRNA sequences shall be as well be sequenced prior to manufacturing and commercialization, to prevent accidental manufacturing errors which may lead to a downstream unwanted side effects in patients.

Q3: describe at least three different potential governance "actions" by considering the four aspects below (Purpose, Design, Assumptions, Risks of Failure & “Success”).

1. Regulate and ban - Regulatory / banning action: Implement a centralized biosecurity and biosafety regulation framework on synthetic DNA manufacturing to prevent accidental or intentional manufacturing of DNA sequences leading to harmful effect to humans or to the environment. This policy shall be implemented at a global regulation by addressing multi-lateral agreements for the fair use of synthetic biology. Under this policy, access to hazardous or dangerous DNA sequences shall be banned or restricted to research institutions under a centralized system.
2. Educate - Community awareness action for scientists, startup companies, and DIY open wetlab grassroot scientists: Expanding awareness of potential biosafety and biosecurity risks in the scientific community. Promoting educational training for future scientists during M.sc. and Ph.D. training courses. The creation of Open Wet Labs and the expansion of startups is a fantastic opportunity to increase access to synbio-fostered creativity and innovation, however, startuppers and DIY open wetlab grass root scientists shall undertake a mandatory training on synthetic biology safety and ethical use .
3. Be transparent - Pipeline transparency action: Mandating DNA manufacturers to keep a log and keep track of which sequences are ordered by whom (e.g. research institutions) and having the database at an international organization to facilitate access by health authorities in case of emergency / side effects. Mandating companies to keep track of sequenced DNA contents within their R&D pipelines. Making DNA synthesis pipelines more transparent and connected to a centralized rapid alert system to prevent misuse or malicious use.