Episome

An episome is a special type of plasmid, which remains part of the eukaryotic genome without integration. Episomes manage this by replicating together with the rest of the genome and subsequently associating with metaphase chromosomes during mitosis. Episomes do not degrade unlike standard plasmids and are not epigenetically silenced inside eukaryotic cell nucleus. Episomes can be observed in nature in certain types of long term infection by adeno-associated virus or Epstein-Barr virus. In 2004, it was proposed that non-viral episomes might be used in genetic therapy for long-term change in gene expression.[1]

As of 1999, there were many known sequences of DNA (deoxyribonucleic acid) that allow a standard plasmid to become episomally retained. One such genetic sequence is S/MAR sequence.[2]

Length of episomal retention is fairly variable between different genetic constructs and there are many known features in the sequence of an episome which will affect the length and stability of genetic expression of carried transgene. Among these features is the amount of CpG sites which contribute to epigenetic sillencing of transgene carried by the episome.[3]

Mechanism of episomal retention

The mechanism behind episomal retention in the case of S/MAR episomes is generally still uncertain. As of 1985, in the case of latent Epstein-Barr virus infection, episomes seemed to be associated with nuclear proteins of the host cell through a set of viral proteins.[4]

References

Conese M, Auriche C, Ascenzioni F (December 2004). "Gene therapy progress and prospects: episomally maintained self-replicating systems". Gene Therapy. 11 (24): 1735–1741. doi:10.1038/sj.gt.3302362. PMID 15385951. S2CID 34565556.
Piechaczek C, Fetzer C, Baiker A, Bode J, Lipps HJ (January 1999). "A vector based on the SV40 origin of replication and chromosomal S/MARs replicates episomally in CHO cells". Nucleic Acids Research. 27 (2): 426–428. doi:10.1093/nar/27.2.426. PMC 148196. PMID 9862961.
Haase R, Argyros O, Wong SP, Harbottle RP, Lipps HJ, Ogris M, et al. (March 2010). "pEPito: a significantly improved non-viral episomal expression vector for mammalian cells". BMC Biotechnology. 10 (1): 20. doi:10.1186/1472-6750-10-20. PMC 2847955. PMID 20230618.
Rawlins DR, Milman G, Hayward SD, Hayward GS (October 1985). "Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region". Cell. 42 (3): 859–868. doi:10.1016/0092-8674(85)90282-X. PMID 2996781. S2CID 9342392.

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[1] Conese M, Auriche C, Ascenzioni F (December 2004). "Gene therapy progress and prospects: episomally maintained self-replicating systems". Gene Therapy. 11 (24): 1735–1741. doi:10.1038/sj.gt.3302362. PMID 15385951. S2CID 34565556.

[2] Piechaczek C, Fetzer C, Baiker A, Bode J, Lipps HJ (January 1999). "A vector based on the SV40 origin of replication and chromosomal S/MARs replicates episomally in CHO cells". Nucleic Acids Research. 27 (2): 426–428. doi:10.1093/nar/27.2.426. PMC 148196. PMID 9862961.

[3] Haase R, Argyros O, Wong SP, Harbottle RP, Lipps HJ, Ogris M, et al. (March 2010). "pEPito: a significantly improved non-viral episomal expression vector for mammalian cells". BMC Biotechnology. 10 (1): 20. doi:10.1186/1472-6750-10-20. PMC 2847955. PMID 20230618.

[4] Rawlins DR, Milman G, Hayward SD, Hayward GS (October 1985). "Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region". Cell. 42 (3): 859–868. doi:10.1016/0092-8674(85)90282-X. PMID 2996781. S2CID 9342392.