They have low immunogenicity and appear to be relatively safe. Plasmid vectors have been used in several angiogenesis gene transfer clinical trials.
Kirk Hammond, in Translating Gene Therapy to the Clinic, 2015 14.4 Vectors and Methods for Cardiac Gene Transfer 14.4.1 Plasmid Vectors The system uses toxic alcohols such as butanol that are detoxified by the Sulfolobus adh gene encoded by the plasmid and the selection provided is weak, possibly because of resident alcohol dehydrogenases encoded by the Pyrococcus spp. The selection marker used is imperfect, however. solfataricus and a replication origin from the Pyrococcus abyssi plasmid pGT5. Another autonomously replicating plasmid, pAG21, contains the adh gene from S. solfataricus under selection for hygromycin resistance. Mutations in the gene that result in increased thermostability of the protein, have allowed two shuttle vectors to be developed for hyperthermophiles: pEXSs, which utilizes a phage SSV1 replication origin, can be propagated in S. Recently, vectors have been developed based on the thermoadapted hygromycin B phosphotransferase gene, which confers resistance to hygromycin at 85 ☌. The current vectors are constructed either with autonomous replication from rolling-circle origins, or else with the ability to integrate into the chromosome using cassette markers flanked by chromosomal DNA fragments to promote homologous replication. Plasmid vectors using puromycin resistance as a selective marker have been developed for many methanogenic Archaea. Robb, in Encyclopedia of Genetics, 2001 Shuttle Vector Systems
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