Principles & Practices - Class 1 Assignment

1. Describe a biological engineering application or tool you want to develop and why

This could be inspired by an idea for your HTGAA class project and/or something for which you are already doing in your research, or something you are just curious about.

Multivirus Resistance (Idea from George Church’s, Regenesis)

The idea is to engineer the human genome in order to become immune to any virus. This would first be done in E.coli bacteria, them agricultural plants and animals and only then, after extensive testing become an option for humans.

Viruses replicate within our cells because they use the same genetic code as we do. If we altered the genetic code of the host cell as well as the ribosome it uses for protein synthesis we could hinder viruses from replicating (therefore eradicating influenza pandemics, common colds, HIV-AIDS, herpes, hepatitis, or polio).

Example:

Different tRNAs transport amino acids to different sets of codons. As we can see in the codon wheel below, there are two different codons that map to the “ter” STOP codon. The RF1 protein handles the process of stopping protein synthesis when the UAG codon is reached. In order to get rid of the RF1 protein, we first have to change all instances of the UAG codon to the UAA codon (which is handled by the RF2 protein). Then we can “safely” remove the gene that encodes for the RF1 protein.

codon.jpeg

Secondly, we take arginine (Arg) and map all AGG and AGA codons to CGA, CGG, CGC and CGU. We can then remove the tRNA that binds, recognizes and translates AGG and AGA. We can further extend this and take leucine, moving all of the CUC and CUU codons to CUA or CUG. Now we have eliminated 5 of the 64 total codons and deleted 3 genes that are normally essential for life.

For a given peptide MRLFV = methionine (M) - arginine (R) - leucine (L) - phenylalanine (F) - valine (V) it would look like this:

Original sequence: AUG AGG CUU UUU GUG UAG

Transformed sequence: AUG CGG CUA UUU GUG UAA

However, the virus would still use the original codons to synthesize the peptide which would not work because the tRNA’s that are needed are no longer available.

What happens if the virus simply mutates and adapts?

Even in the best case scenario where the virus has a small genome (less chance of containing a removed codon), a high mutation rate (to adapt to the new way of coding) and there exists a large viral population (more shots to target) it would be highly unlikely that the virus adapts in time. (1 in 10^28 would manage to still infect the host cell)