They are major problems. In experimental animals, the simplest way of adding genes is to microscopically inject DNA into a one-cell embryo. While it gets the job done, this approach has big drawbacks, including its unpredictability. The genes land randomly along the cell's chromosomes. In the wrong place, they work poorly or not at all, or they fall disastrously into the middle of some essential gene, crippling it.
Scientists add DNA to a plate of embryonic cells.
When all goes well, the new genetic material lines itself up beside the similar-looking stretch of DNA it needs to replace, then makes the switch. However, the idea of actually changing a human's inborn genes gives many scientists the willies. They would rather talk about adding extra genes and leaving the original set alone. One way to do this is to build an artificial chromosome, something already tested in animals. The chromosome would have no genes of its own.