Limits of gene editing

Question

I was reading some articles about CRISPR and the world of gene editing, but then a lot of questions for which I couldn't find any answer online came into my mind. Those are all about how far can we edit an organism. So here is the general question, followed by some other to narrow down a little bit this broad subject:

What are the limits of gene edition?

1. Can one edit the genes in its entire body? (as a human, or a multicellular organism)
2. What are the risks? I heard that some people who did try gene therapy ended up having some of their modified cells turned into cancer. Was is because of gene incompatibility or because of error during the gene editing process?
3. Can we go as far as adding some chromosomes or changing an entire chromosome? For example, if a male human would like to change their sex, could they switch all their Y to an X?

EDIT: I decided to accept the answer from @MattDMo. However, I'm still interested in some development (clues with other technologies...)

Answer 1

Your question is very broad, but I'll try to address each of your points briefly.

1. It would be nearly impossible to edit the genes in every cell of a human being or other complex organism simply due to the number (and accessibility) of cells. A full-grown human has in the neighborhood of 30 trillion cells - 30,000,000,000,000. Cells in locations such as the brain and central nervous system are protected by the blood-brain barrier, which would keep most gene therapy vectors from accessing those cells. There are other reasons why editing each cell in the body is virtually impossible, such as vectors accumulating in the liver, but this is one of the main ones.

2. Cancer is indeed a risk from gene therapy in general, although DNA editing technologies like CRISPR in particular have a lower risk due to thTe circumstances surround exactly how the therapy is delivered to the nucleus of the cell where DNA resides. Other risks include potentially serious or fatal systemic inflammation due to an immune reaction to the viral vector which carries the CRISPR "machinery". Off-target effects can occur due to the wrong cells being targeted (although this risk is generally lower with CRISPR). Additionally, there is the very small but non-zero chance that the genetically-engineered vector could somehow regain its native infectious capability. Newer generations of gene therapy have significantly reduced this chance, however.

3. Very briefly, no. DNA is made up of "letters" (A, T, C, and G) called bases or base pairs, and typical CRISPR constructs only operate on 10-20 bases at the most — usually it's just one or a couple that are changed. A typical human chromosome has millions of base pairs encompassing hundreds to thousands of genes, so editing, adding, or removing an entire chromosome is simply out of the realm of possibility with this technology.