HTGAA: Genome Engineering

Class Material

Grand Scale Genome Engineering of Viruses, Bacteria, and Eukaryotes

News of the COVID-19 pandemic dominates all media. There is lots of material about possible scientific solutions to help mitigate the disease. Many university and industrial scientific groups have shifted their attention to this new problem. Imagine that you are a scientist told by your advisor or boss to come up with a plan to make a difference. Possible ways to go about this include therapeutic drugs (small molecules like nucleoside analogs or biologicals like enzymes, antibodies, or nucleic acids), new vaccines, or new or better diagnostics. Here is your assignment:


  1. Describe your new product. Do this using 6 sentences or less.
  2. I used to work in the pharmaceutical industry on developing new therapeutics to treat infectious diseases. One thing that was drilled into us was that it takes 3000 days to get a new drug to market once it has been discovered. That’s about 8 years. During that time things like toxicology studies using animals, pharmacokinetics, and plans for large scale synthesis of the drugs are the first things determined. Then there are Phase !, II, and III clinical trials to do. Under ordinary circumstances, every day is precious because a new drug or vaccine patent life diminishes while all this research is going on. Now haste is even more important because we are in a pandemic, and people are dying. If you roam around the internet, you will see that there are ways to accelerate some of these processes. President Trump talks about having a vaccine in a few months. That seems farfetched, but as I mentioned in the lecture, Moderna is already testing a mRNA-based vaccine against the corona virus. Many companies are developing new diagnostic approaches. Provide a bullet point outline of the steps needed to get your product approved by the US FDA and into clinical use. Be brief, my goal here is that you gain some understanding of the regulatory processes for medical solutions to a problem like the current pandemic.
  3. How would your approval process be different if you were developing a product for a new rabies vaccine (i.e. something that was not urgent)? Try to write this in six sentences of less.

One of the most unexpected findings from the JCVI minimal bacterial cell project was that almost one third of the genes (149 of 473) encoded proteins of no known function.



Why do so many of the essential genes have no known function? I offer a possible clue. Look at the dendogram below. It is based on 16S rRNA sequences. Make a hypothesis using this clue or offer an idea or ideas of your own.


As stated above, in the minimal cell JCVI-syn3.0, 149 of 473 genes made products of unknown function. That is about 31%. Would the predecessor of JCVI-syn3.0, wild type Mycoplasma mycoides have a higher percentage of unknown function genes? Why? How about for Escherichia coli, the most studied of all bacteria. Would it have a higher fraction of genes of unknown function? Why? Short answers to the why questions are acceptable.


In an age where scientists like us can design and build new organisms and viruses, what is acceptable and non-acceptable research? When Eckard Wimmer synthesized a poliovirus genome to produce virus from digital information or David Evans made horsepox virus with a synthetic genome there was a public outcry and widespread condemnation. The same happened when my JCVI team constructed a bacterium with a synthetic genome. Consider the HTGAA class with Megan Palmer and how it relates to what we know is possible and likely to be possible.


Related Readings & References


I offer more articles than you will be able to get through. They are organized by topic and more or less in the same order the topic are introduced in the lecture. Unless you are more motivated than I think necessary for the HTGAA class, I suggest you read just for concepts, not for experimental details.

Reverse Genetics of Viruses and Using Synthetic Biology to address COVID-19