CRISPR-mediated biocontainment

We have exploited the repetitive nature of transposable elements of the human genome to generate synthetic circuits. Transposable elements such as LINE-1 and Alu have successfully replicated in mammalian genomes throughout evolution to reach a copy number ranging from thousands to more than a million. Targeting these repetitive elements with programmable DNA nucleases such as CRISPR-Cas9 rapidly induce extremely high levels of cell death. We use this genotoxic feature to build synthetic biocontainment circuits: CRISPR defense system (CRISPR-DS) capable of preventing CRISPR genome editing, and we introduce the proof-of-concept of CRISPR Safety-Switch, an inducible, stringent and non-leaky kill-switch capable of clearing out cell lines resistant to DNA breaks.

Enabling large-scale genome editing at repetitive elements by reducing DNA nicking

To extend the frontier of genome editing and enable editing of repetitive elements of mammalian genomes, we made use of a set of dead-Cas9 base editor (dBE) variants that allow editing at tens of thousands of loci per cell by overcoming the cell death associated with DNA double-strand breaks and single-strand breaks. We used a set of gRNAs targeting repetitive elements-ranging in target copy number from about 32 to 161 000 per cell. dBEs enabled survival after large-scale base editing, allowing targeted mutations at up to ∼13 200 and ∼12 200 loci in 293T and human induced pluripotent stem cells (hiPSCs), respectively, three orders of magnitude greater than previously recorded. These dBEs can overcome current on-target mutation and toxicity barriers that prevent cell survival after large-scale genome engineering

Starting a Medical Technology Venture as a Young Academic Innovator or Student Entrepreneur

Following the footprints of Bill Gates, Steve Jobs and Mark Zuckerberg, there has been a misconception that students are better off quitting their studies to bring to life their ideas, create jobs and monetize their inventions. Having historically transitioned from manpower to mind power, we live in one of the most rapidly changing times in human history. As a result, academic institutions that are supposed to be pioneers and educators of the next generations have started to realize that they need to adapt to a new system, and change their policies to be more flexible towards patent ownership and commercialization. There is an infrastructure being developed towards students starting their own businesses while continuing with their studies. This paper aims to provide an overview of the existing landscape, the exciting rewards as well as risks awaiting a student entrepreneur, the challenges of the present ecosystem, and questions to consider prior to embarking on such a journey. Various entities influencing the start-up environment are considered, specifically for the medical technology sector. These parties include but are not limited to: scientists, clinicians, investors, academic institutions and governments. A special focus will be set on the seemingly unbridgeable gap between founding a company and a scientific career. Keywords: Entrepreneurship, Bioentrepreneur, Student entrepreneurship, Medical device