[MUSIC] >> One important and growing component of synthetic biology in human health is human genetic modification. When you're considering changing DNA there are a couple of different variables, right? There is the different kind of target DNA, so you're talking about somatic DNA, so DNA of the body cells. Germline DNA, so DNA in sperm, eggs, or embryos. Or modifications of the mitochondrial DNA. There are also different methods or techniques that you can use including gene transfer. Genome editing and mitochondrial DNA transfer which for our purposes I'm going to leave off the table. So I want to first talk about somatic applications of gene transfer. So we have been doing gene transfer, some call it gene therapy for quite some time now. First trial began in the early 1990s. And this is, gene transfer is the delivery of a therapeutic transgene to treat a particular patient. And historically we've done this to treat single-gene defects but that's expanding. And today in the US. We've had around 450 clinical trials, so a lot of experience with gene transfer. A change in genetic modification in recent years though, has to do with Genome editing technologies. In the past, modification of DNA was extremely inefficient. You were either looking at breeding, in nonhuman animals, hard to do controlled breeding experiments in humans. Or something like radiation or a DNA interpolation agent that would cause lots of mutations followed by selection of the mutants that you're interested in, the difference with the new genome editing technologies is that they're very specific, they're not perfect yet but they're very specific. So, rather than doing whole scale mutation followed by selection, you can in fact go in and make the particular mutation that you are interested in. There are several different kinds of Genome Editing technologies in use right now, this includes Zinc finger nucleases. Which have been around for quite some time and were discovered in 1996. Transcription activator-like effector nucleases which everyone calls TALENs and clustered regularly interspaced short palindromic repeats otherwise known as CRISPR. Which came on the scene in 2012 and has taken off like wild fire. Genome editing technologies can be deployed either for dealing with somatic DNA or modifying DNA or germline DNA. It can be used for reverse genetics. Rather than forward genetics where you identify a phenotype and you study the genetics. In reverse genetics you break things and look fro the phenotype. In genome again, genome editing is a huge advance of a past mute genesis strategies. Genome editing can be used in gene therapy or gene transfer. >> Mm-hm. >> Talked about before though there have been a number of several examples now of genome editing being used in gene transfer. One small trial using zinc finger nucleases to modify. Anthologist T cells for CCR5, to look at HIV infection. Also there are been a couple instances of using Genome Editing in cancer. One with an older technology in a young girl who had cancer and was failing other treatments. And then recently, the first trial using CRISPR to treat lung cancer. And then the truly sort of controversial application of genome editing in human health has to do with human germ line genetic modification. So the idea that you could use this technology, apply it to Germline DNA, and create human genetic modifications. Not just in a person in front of you, but in generations to come. And this is particularly interesting at this time in science because there's a convergence of genome editing with Pluripotent stem cell technology. So, you can take a somatic cell in an individual, you can give it a little fountain of youth potion, turn it back to a Pluripotent cell, that is a cell that can turn to any of the 220 odds cells types of the human body. And then you can create Agon's sperm for that, in theory. You can do genome, you deploy con the cell. Was creating germline genetic modifications in humans. As I will talk about later in this week's material there's been a lot of discussion and debate about this particular application of this technology. So genomic editing, and in particular CRISPR is much more specific as I've noted than things that have come before it. But there are still some off target effects and concerns about mosaicism. So this is where you deploy the technology you modify the gene appropriately in some but not all cells. And scientists are still working on refining the technology.
