I was surfing around reading about Sangamo's Zinc Finger Protein Transcription Factor (aka 'gene editor'), and ended up on their website:
http://www.sangamo.com/index.php
I just want to better understand how this thing works, and what its weaknesses/limitations are.
Their transcription factor is made of 2 main components (domains). The first is the binding/recognition domain, to properly target the right area of the genome. The second is the functional domain, which is basically the gene you're trying to insert (can even be a knocked-out gene, if you're trying to disable rather than enable something). This apparently is how natural transcription factors work.
What worries me is suppose the binding domain makes a mistake? Seems to me that if if you have some unrelated genomic region that matches most of the binding sequence, there's a chance of the binding sequence still attaching to that genomic site. So I'd think you'd really want detailed information on a patient's genomic sequence before you try to alter it.
I'd like to know just how big a sequence can you slap in there? At what point does this method become unreliable?
What are things that help or favor this technique working correctly?
What is the epigenetic impact? From what you've told me, the methylation regulatory stuff only applies to the promoter portion of a gene sequence, so it sounds to me that if you don't mess with the promoter portion, you're not going affect the epigenetic side of things. Correct?
What are the various possible ways in which this thing can go wrong, and cause problems?
