A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2019; you can also visit <a rel="external noopener" href="http://pdfs.semanticscholar.org/9573/f52c64dc188119337c6b5ab77888509b7cfb.pdf">the original URL</a>. The file type is <code>application/pdf</code>.
<i title="Elsevier BV">
<a target="_blank" rel="noopener" href="https://fatcat.wiki/container/mqphuanj5jg4xg6zto77tafyra" style="color: black;">Molecular Therapy</a>
We have constructed plasmid DNA vectors that contain Epstein-Barr virus (EBV) sequences and the human gene (SERPINA1) encoding ␣ 1 -antitrypsin (AAT). We demonstrate that a plasmid carrying the full SERPINA1 on a 19-kb genomic fragment and the EBV gene EBNA1 and its family of repeats binding sites undergoes efficient extrachromosomal replication in dividing mammalian tissue culture cells. Therefore, use of a whole genomic therapeutic gene to provide both replication and gene expression may be<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1006/mthe.2001.0429">doi:10.1006/mthe.2001.0429</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/11482983">pmid:11482983</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/bkfrbsbh2vgz3juabhfwepzdcu">fatcat:bkfrbsbh2vgz3juabhfwepzdcu</a> </span>
more »... effective gene therapy vector design, if the target cells are dividing. The efficacy of this same vector for expression of AAT in vivo in the nondividing cells of mouse liver was determined by hydrodynamic injection of naked plasmid DNA by means of the tail vein. A single injection of an EBV/genomic SERPINA1 vector provided Ͼ 300 g/ml of AAT, which approached normal plasma levels and persisted for the Ͼ 9-month duration of the experiment. These data exceed most previously reported values, probably due to sequences in the genomic DNA that resist silencing of gene expression, possibly in combination with favorable effects on expression provided by the EBV sequences. These results demonstrate that plasmid DNA with the correct cis-acting sequences can provide in vivo long-term expression of protein at high levels that are therapeutically relevant for gene therapy.
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190228164857/http://pdfs.semanticscholar.org/9573/f52c64dc188119337c6b5ab77888509b7cfb.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/95/73/9573f52c64dc188119337c6b5ab77888509b7cfb.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1006/mthe.2001.0429"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> Publisher / doi.org </button> </a>