GENOME 222FS Lecture 24: GENOME 222FS Lecture 24

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Engineered chromosomes containing native or synthetic dna. 6 to 10 mb in size (1/10th to 1/5th the size of a native chromosomes) Could be used for gene therapy to express one or multiple genes (>50 kb) Can be used to study requirements and characteristics of the centromere function, chromosome stability (aneuploidy), and chromatin dynamics. But centromeres have a shared chromatin structure involving the histone variant cenp- Two major approaches: top-down approach, bottom-up approach. Requires chromosome transfer to a chicken cell line (mmct) Both arms of the chromosome are truncated. Chromosomes are transferred again into human cells (mmct) Can be transferred through germline in mice (mmct) Challenge: moving the hac around to different cells. More recently developed (2nd and 3rd generation) hacs are better suited for gene therapy and epigenetic studies. Hacs that have teto arrays have multiple experimental purposes. Using hacs for gene therapy: attributes of an ideal gene therapy vector. Not limited to any constraints on gene size.

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