Genome Engineering: Leveraging 3D Printing for Biofabrication
May 9, 2019
This week, we considered methods of modifying larger segments of the genome, perhaps via the introduction of artificial chromosomes. The J. Craig Venter institute is looking to create artificial life from scratch by creating and inserting entire chromosomes. To do this, they must identify the genes necessary for creating life. Two large categories of the functions they need to include are genetic information processing and metabolism. Included in genetic information processing is trascription, translation, and DNA replication. Included in metabolism is ATP synthesis and protein, lipid, and carbohydrate production/breakdown. Other important functions include reproduction and transporting molecules.
In order to be inserted into a bacteria, the synthetic chromosome must be able to physically pass through the cell wall and membrane, to be recognized as "self" such that the bacteria does not destroy it using a Cas9 immune response, and to contain promoters that enable it to be read by the current bacterial mechanisms. In order to be inserted into mammalian cells, it would require some physical insertion, epigenetic matching, and promoter matching.
Instead of entire genome transplantation, one could use a CRISPR like system to directly target sequences that share certain patterns-using CRISPR's potential lack of specificity to its benefit. Current genetic editing techniques are either highly unspecific (such as randomly mutating and selecting for a trait) or overly specific (adding/modifying a select and small nummber of genes via CRISPR or transformation). The only technique I can think of that would easily affect the entire genome is cloning, which involves removing all genetic material and inserting an entirely new genome. In eukaryotic cells, this is done by adding and removing the entire nuclei.