Short Communication

Gene Therapy (2013) 20, 1022–1028; doi:10.1038/gt.2013.27; published online 30 May 2013

2-diethylaminoethyl-dextran methyl methacrylate copolymer nonviral vector: still a long way toward the safety of aerosol gene therapy

P Zarogoulidis1,2, W Hohenforst-Schmidt3, K Darwiche2, L Krauss4, D Sparopoulou5, L Sakkas6, A Gschwendtner7, H Huang8, F J Turner9, L Freitag2 and K Zarogoulidis1

  1. 1Pulmonary Department-Oncology Unit, ‘G. Papanikolaou’ General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
  2. 2Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany
  3. 3II Medical Clinic, Coburg Hospital, University of Wuerzburg, Coburg, Germany
  4. 4CytoViva Inc., Auburn, AL, USA
  5. 5Experimental Animal Laboratory, ‘Theiageneio’ Anticancer Hospital, Thessaloniki, Greece
  6. 6Department of Pathology, ‘G. Papanikolaou’ General Hospital, Thessaloniki, Greece
  7. 7Department of Pathology, Clinic of Amberg, Amberg, Germany
  8. 8Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, China
  9. 9Pulmonary Department, Clinical Research, Nevada Cancer Center, Las Vegas, NV, USA

Correspondence: Dr P Zarogoulidis, Pulmonary Department-Oncology Unit, ‘G. Papanikolaou’ General Hospital, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece. E-mail: pzarog@hotmail.com

Received 22 March 2013; Revised 15 April 2013; Accepted 24 April 2013
Advance online publication 30 May 2013

Top

Abstract

Revealing the lung tumor genome has directed the current treatment strategies toward targeted therapy. First line treatments targeting the genome of lung tumor cells have been approved and are on the market. However, they are limited by the small number of patients with the current investigated genetic mutations. Novel treatment administration modalities have been also investigated in an effort to increase the local drug deposition and disease control. In the current study, we investigated the safety of the new nonviral vector 2-diethylaminoethyl-dextran methyl methacrylate copolymer (DDMC; Ryujyu Science), which belongs to the 2-diethylaminoethyl-dextran family by aerosol administration. Thirty male BALBC mice, 2 month old, were included and divided into three groups. However, pathological findings indicated severe emphysema within three aerosol sessions. In addition, the CytoViva technique was applied for the first time to display the nonviral particles within the pulmonary tissue and emphysema lesions, and a spectral library of the nonviral vector was also established. Although our results in BALBC mice prevented us from further investigation of the DDMC nonviral vector as a vehicle for gene therapy, further investigation in animals with larger airways is warranted to properly evaluate the safety of the vector.

Keywords:

vectors; aerosol therapy; lung cancer