From Tamara, our resident science correspondent…

Hi friends,

Niko and crew have been getting lots of requests from friends and family to explain the nitty gritty details of the trial so they asked me to take a stab at it.

Tomorrow, if all goes well, Dr. Liau will perform a biopsy of the tumor growing in Niko’s brain. Once a neuropathologist confirms that the tumor is what everyone thinks it is, Dr. Liau will take four more small biopsies in order to create a small pocket within the tumor. She will then inject a very neat virus into the tumor, stitch him up and wait a couple weeks for the virus to play the role of a trojan horse by inserting a new gene whose protein product converts a harmless anti-fungal drug into a highly toxic chemotherapeutic agent - but only in infected tumor cells! This targeted treatment has a ton of benefits compared to traditional chemos that act like hammers, killing healthy and tumor cells alike.

The Toca virus is a single stranded RNA molecule that encodes the entire viral genome plus one important addition – the trojan horse, but more on that later. The virus is packed into a viral envelope along with some key viral proteins that enable it to infect cells, integrate its genome into the host genome and REPLICATE. Part of what makes this approach so great is that the virus can only integrate its genetic material into dividing cells – IE the tumor. 

OK, so what exactly does this Toca virus do and why are we so keen to inject it into Niko’s brain? When the virus infects cells, it releases the viral genome plus its protein goodies into the cytoplasm of the cell. There, a viral protein reverse transcribes the RNA genome of the virus into DNA. Here’s the trick though, the newly created DNA only makes it as far as the cytoplasm, but to integrate into Niko’s genome, it needs to get to the nucleus. The only way that happens is if a cell divides. Overwhelmingly, the types of cells dividing in this particular area of Niko’s brain are tumor cells. Once it makes it into the nucleus of the tumor cells, another viral protein inserts the viral DNA into Niko’s DNA (thus GMO Niko!). Now the tumor cells start copying the viral DNA which is used to ultimately make more viral RNA and infection proteins so the virus can get packed up and go forth to infect more and more and more tumor cells*. 

Importantly, the engineered virus was designed to be a trusty steed. Hidden in its horsey bowels, the trojan horse carries a gene that comes from yeast called Cytosine Deaminase or CD. The CD gene encodes a CD protein on steroids because it too has been fiddled with, in this case to make the protein product tougher, more effective and longer- lasting. The CD protein converts a completely safe and non-toxic anti-fungal drug called 5-FC to one of the most potent chemotherapeutic agents called 5-FU. 5-FU kills cells dead by inhibiting a protein called thymidylate synthase that functions to make deoxythymidine – one of the four main building blocks of DNA (the T in ATCG). If cells can’t make T bases, they are unable to replicate and die. 

I know the title of this post reads “GMO Niko!” but it’s actually a partial misnomer. Not all of his cells will be genetically modified by the virus – just a subset of cancer cells.  So really, Niko will become mosaic GMO Niko - in other words, extraordinarily special, genetically and otherwise.

Here’s hoping the Trojan horse ends the siege and kills this thing Greek style. 

Tamara

*Follow the link to a neat animation that shows how another RNA virus – HIV – infects cells and replicates:http://www.galaxygoo.org/biochem/hiv/hiv_lifecycle.html