The Open Gene Therapy Journal (Open Gene Ther J)

Publications in this journal

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  Available from: benthamscience.com

  Article: Ceiling culture-derived proliferative adipocytes are a possible delivery vehicle for enzyme replacement therapy in lecithin: cholesterol acyltransferase deficiency

  Masayuki Kuroda, Yasuyuki Aoyagi, Sakiyo Asada, Hideaki Bujo, Shigeaki Tanaka, Shunichi Konno, Masami Tanio, Itsuko Ishii, Kazuhiko Machida, Fumiaki Matsumoto, Kaneshige Satoh, Masayuki Aso, Yasushi Saito
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  ABSTRACT: Human proliferative adipocytes propagated via ceiling culture technique from subcutaneous fat tissue (desig-nated as ccdPA) were herein evaluated for their potential as a recipient for retroviral vector-mediated gene transduction of a therapeutic protein delivery. Exposure to the ZsGreen-expressing vector supernatant using a cell preparation generated by a 7-day ceiling culture induced a 40-50% transduction efficiency, with less than two integrated copies of viral genome per cell on average. The lcat gene-transduced human ccdPA secreted functional LCAT protein, correlating with the inte-grated copy number of vector genome. The gene-transduced cells could be expanded up to nearly 10 12 cells from 1 g of fat tissue within one month after fat tissue preparation. The cells also maintained the potential to differentiate into adipocytes in vitro. The presence of human LCAT protein in serum was immunologically identified upon transplantation of lcat-expressing ccdPA into the adipose tissue of immune-deficient mice. These results indicated that human ccdPA has a novel therapeutic potential for LCAT-deficient patients. The clinical application in combination with cell transplantation shed a light on a development of a life-long protein replacement therapy for LCAT-deficient patients.
  The Open Gene Therapy Journal 01/2011; 4.
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  Available from: benthamscience.com

  Article: Adenovirus Release from the Infected Cell as a Key Factor for Adenovirus Oncolysis

  Alena Gros, Sonia Guedan
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  ABSTRACT: Adenovirus release is not triggered until late times after viral infection, when the adenovirus death protein (ADP) accumulates to induce viral egress. Thus, the natural rate of adenovirus release may hinder the spread of oncolytic adenoviruses. Several experimental approaches have provided evidence indicating that promoting adenovirus release can be used to enhance their therapeutic potential. This review briefly summarizes what is known about the mechanism of adenovirus release and describes three different strategies, ADP overexpression, apoptosis induction, and bioselection, which can be used to enhance adenovirus release. Finally we will discuss some of the future perspectives that will contribute to the better use of progeny release for the improvement of the antitumor activity of oncolytic adenoviruses.
  The Open Gene Therapy Journal 01/2010; 3:24-30.
• Article: Enhanced Gene Delivery to Human Primary Endothelial Cells Using Tropism-Modified Adenovirus Vectors.

  Meredith A Preuss, Joel N Glasgow, Maaike Everts, Mariam A Stoff-Khalili, Hongju Wu, David T Curiel
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  ABSTRACT: Endothelial cells have been noted to have relatively low expression of the native receptor for adenovirus serotype 5 (Ad5), coxsackie and adenovirus receptor (CAR), and are thus refractory to Ad5 infection. In this study, we hypothesize that increases in the infectivity of Ad5 in primary human pulmonary artery (HPAEC), coronary artery (HCAEC) and umbilical vein endothelial cells (HUVEC) can be achieved through genetic capsid modification of Ad5 to bypass CAR-dependent infection. The modifications tested in this study include incorporation of an integrin-binding RGD peptide motif (Ad5.RGD), a poly-lysine motif (Ad5.pK7), a combination of both of these peptide domains (Ad5.RGD.pK7), an adenovirus serotype 3 knob domain (Ad5/3Luc1) and canine adenovirus serotype 1 or 2 knob domains (Ad5Luc1-CK1 and Ad5Luc1-CK2). In HPAEC and HCAEC, the greatest infectivity enhancements were achieved using Ad5/3Luc1 (26-fold and 30-fold respectively). HUVEC was most readily infected by Ad5Luc1-CK1 (213-fold). These results demonstrate that gains in Ad5 infectivity in endothelial cells can be accomplished with genetic capsid modifications.
  The Open Gene Therapy Journal 01/2008; 1:7-11.