The ability to deliver exogenous DNA to mammalian cell lines is a fundamental tool in the development of advanced therapeutics, vaccines, and cellular diagnostics, as well as for basic biological and biomedical research… The successful development of technologies for rapid introduction of large DNA vectors into human cell lines will enable the ability to engineer much more complex functionalities into human cell lines than are currently possible.
A human artificial chromosome (HAC) is a microchromosome that can act as a new chromosome in a population of human cells. That is, instead of 46 chromosomes, the cell could have 47 with the 47th being very small, roughly 6-10 megabases in size, and able to carry new genes introduced by human researchers.
These include random DNA insertion into the host genome, variation in stable integration sites between cell lines, variation in the copy number and expression level of DNA that is delivered, limitations on the number and size of DNA constructs that can be delivered, and immunological responses to foreign DNA.
The phrase ‘genome-scale engineering’ invokes a future in which organisms are custom designed to serve humanity. Yet humans have sculpted the genomes of domesticated plants and animals for generations. Darwin’s contemporary William Youatt described selective breeding as ‘that which enables the agriculturalist, not only to modify the character of his flock, but to change it altogether. It is the magician’s wand, by means of which he may summon into life whatever form and mold he pleases’ (Youatt, 1837).