ADENOVIRUS VECTOR-TRANSDUCED HEPATOCYTES IMPLANTED VIA A PREFORMED COLLAGEN PTFE SUPPORT PERSIST FOR AT LEAST 4 WEEKS IN-VIVO/

Citation
Ej. Kremer et al., ADENOVIRUS VECTOR-TRANSDUCED HEPATOCYTES IMPLANTED VIA A PREFORMED COLLAGEN PTFE SUPPORT PERSIST FOR AT LEAST 4 WEEKS IN-VIVO/, Gene therapy, 3(10), 1996, pp. 932-936
Citations number
39
Categorie Soggetti
Pharmacology & Pharmacy","Genetics & Heredity",Biology
Journal title
ISSN journal
09697128
Volume
3
Issue
10
Year of publication
1996
Pages
932 - 936
Database
ISI
SICI code
0969-7128(1996)3:10<932:AVHIVA>2.0.ZU;2-F
Abstract
Liver-directed gene therapy has the potential to provide an effective adjutant to conventional treatments for liver diseases. In vivo gene t ransfer is promising but still effectively out of reach with conventio nal gene delivery techniques, Ex vivo gene therapy using hepatocyte tr ansplantation, however, has been encouraging. We describe an approach toward treatment of liver-related diseases by combining several of the advantageous properties of current liver-directed therapies. Primary hepatocytes were isolated, transduced with an adenovirus vector Encodi ng a reporter gene, embedded in a collagen/polytetrafluoroethylene (PT FE) lattice, and implanted in mice. Recovered 'hepatocyte-organoids' w ere assayed for the presence and viability of the implanted hepatocyte s, duration of transgene expression and presence of the adenovirus vec tor. In an initial attempt, we demonstrate that genetically modified h epatocytes can survive and express a transgene for at least 4 weeks in vivo when embedded in a collagen/PTFE support and implanted in the in traperitoneal cavity. This approach takes advantage of hepatocyte-spec ific functions in order to treat diseases where a fraction of the norm al enzymatic activity is sufficient to alleviate a disease phenotype.