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.[7] Progress regarding de novo HAC formation has been limited, as many large genomic fragments will not successfully integrate into de novo vectors.[2] Another factor limiting de novo vector formation is limited knowledge of what elements are required for construction, specifically centromeric sequences.[3]