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A few years ago, the Thought Emporium published a video (https://www.youtube.com/watch?v=aoczYXJeMY4) in which he refers to a study in which they mix plasmid DNA with Chitosan and feed it to mice to express LacZ gene so the mice's intestines could produce Lactase (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717060/?fbclid=IwAR0K7C8GounA9DZwkIRm8qSGMSKuo_uHsl8-2qd2fGjnIgn5SkPXddcODsY).

Thought Emporium then shows a plasmid that could do the same for humans. In the plasmid (image below), there is this "SMAR" sequence. He says this acts like an ori but for mammalian cells.

I don't understand how SMAR functions like an ori. When I look up SMAR, it seems to be a protein structure in the nucleus rather than a gene. And the original paper doesn't mention SMAR at all.

What is SMAR? How does it function? Why does it act like an ori?

enter image description here

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    $\begingroup$ Sequence for plasmid here says that it is ncRNA. It is added as in the cassette with the Lactase, so will likely be as one RNA, possibly as a nuclear localization signal or something $\endgroup$
    – bob1
    Commented Sep 22, 2022 at 23:41

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S/MAR (nuclear scaffold/matrix attachment region) Is a DNA sequence pattern that recruits the nuclear protein hnRNP-U/SAF-A a multifunctional scaffold/matrix specific factor.

Jenke et al. 2002

Immunoprecipitation of the crosslinked DNA–protein complex demonstrates that pEPI-1 is bound to this protein [SAF-A] in vivo. These data provide the first experimental evidence for the binding of an artificial episome to a nuclear matrix protein in vivo and the basis for understanding the mitotic stability of this novel vector class.

Jenke et al. 2004 confirmed their previous finding and shows that a tetramer of a 155 bp region together with upstream transcriptional activity is sufficient for mitotic stability (mediated by SAF-A).

It seems to me that the sequence of SMAR is the binding surface for an adapter protein that elevates foreign DNA to a chromosome-like state. It was also shown that SMAR handles chromosome-associated processes like nuclear localization, S-Phase, etc. (Stehle et al. 2007

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