There are currently two accepted models for the creation of human artificial chromosome vectors. The first is to create a small minichromosome by altering a natural human chromosome. This is accomplished by truncating the natural chromosome, followed by the introduction of unique genetic material via the Cre-Lox system of recombination. The second method involves the literal creation of a novel chromosome de novo. Progress regarding de novo HAC formation has been limited, as many large genomic fragments will not successfully integrate into de novo vectors. Another factor limiting de novo vector formation is limited knowledge of what elements are required for construction, specifically centromeric sequences. However, challenges involving centromeric sequences have begun to be overcome.