Cosmid

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A cosmid is a hybrid DNA molecule that behaves like a plasmid but carries a Lambda phage cos site. It is used as a cloning vector in genetic engineering and for making genomic libraries. Cosmids were first described in 1978. They can hold large DNA fragments, about 37 to 52 kilobases (kb), typically around 40–45 kb, which is bigger than ordinary plasmids but smaller than whole chromosomes.

Cosmids can replicate as plasmids in bacteria if they have a suitable origin of replication (ori), such as ColE1 for bacterial replication or SV40 origin for mammalian cells. They usually include an antibiotic resistance gene so that cells carrying the cosmid can be selected by growing on antibiotic-containing media. In addition to their plasmid features, cosmids have one or more lambda cos sites, which allow the DNA to be packaged into phage heads for delivery into cells.

In vitro packaging uses cohesive ends at the cos sites to fit the cosmid DNA into a phage head. The cosmid DNA (and not the empty vector) is packaged, and the resulting particles can transfer the DNA into bacteria by transduction. Because packaging requires a sufficiently large insert, vectors without DNA inserts are not packaged. The mechanism helps reduce unstable or problematic DNA sequences, such as many repeats. Cosmids are usually used as plasmids with a bacterial origin, antibiotic marker, and cloning site, plus one or more cos sites derived from lambda phage. There are different types, including broad-host-range cosmids, shuttle cosmids, and mammalian cosmids that carry SV40 origin and mammalian selectable markers.

The typical loading capacity is around 40 kb. To construct a library, researchers cut the target genomic DNA into pieces, ligate the fragments into the cosmid vector arms, and then use in vitro packaging to introduce the recombinant cosmids into E. coli. Clones form colonies (not plaques), with a relatively low clone density of about 10^5–10^6 colonies per microgram of ligated DNA. Commercial examples include systems like SuperCos1.

Overall, cosmids offer a way to clone and study large chunks of DNA while combining features of plasmids and phage vectors.