episomale

Episomal, or episomale, refers to DNA elements that reside and replicate independently of the host cell’s chromosomal DNA. In many organisms, episomes are circular DNA molecules that can exist as extrachromosomal plasmids in bacteria or as latent elements in eukaryotic cells. The term emphasizes that replication and inheritance do not require chromosomal integration.

In bacteria and yeast, episomes include plasmids such as bacterial plasmids and the yeast 2-micron plasmid. Eukaryotic viral genomes can persist episomally, as with the Epstein-Barr virus (EBV) episome in B lymphocytes, maintained by the viral origin oriP and the EBNA1 protein. In human cells, human papillomavirus (HPV) can also persist as episomal DNA, though integration into the host genome can occur during carcinogenesis. Episomal maintenance is facilitated by replication origins and, in some cases, host- or virus-encoded maintenance systems.

Maintenance and replication: Episomal DNA carries its own replication origin (ori) and sometimes specific maintenance elements. In dividing cells, copy number and distribution to daughter cells are controlled by replication timing, partitioning mechanisms, and tethering to the nuclear architecture. Because episomal DNA is not integrated, its copy number can fluctuate and it may be lost without selective pressure.

Applications: Episomal vectors are used in research to express genes transiently or stably without integration, reducing the risk of insertional mutagenesis. In gene therapy and vaccines, episomal vectors aim for durable expression with a lower risk of genomic disruption, though dilution during cell division and potential epigenetic silencing limit long-term expression. Elements such as scaffold/matrix attachment regions (S/MARs) and viral-origin systems have been explored to improve stability.

Limitations: Expression levels can vary, host range may be restricted, copy-number control can be imperfect, and there is potential for immune responses or silencing over time.