Ex vivo transduction of human dermal tissue structures for autologous implantation production and delivery of therapeutic proteins.
Systemic delivery of therapeutic proteins through gene transfer approaches has been carried out mostly by ex vivo transduction of single cells or by direct in vivo injection of an expression vector. In this work an intact miniature biopsy of human dermis (microdermis) is harvested and transduced ex vivo by a viral vector encoding a gene for the therapeutic protein. The microdermis preserves its three-dimensional structure and viability during the ex vivo manipulations. Furthermore, upon transduction with adenoviral and adeno-associated viral vectors the microdermis secretes recombinant human erythropoietin (hEPO). Biochemical analysis of the secreted hEPO showed similarity to the clinically approved recombinant hEPO. Subcutaneous implantation of microdermal hEPO into SCID mice exhibited hEPO secretion in the blood circulation and preserved elevated hematocrit for several months, demonstrating the technology's potential for sustained delivery of protein therapeutics.
Brill-Almon
Einat
E
Medgenics, Inc., Biogenics Ltd., Teradion Business Park, Misgav, Israel.
Stern
Baruch
B
Afik
Daniel
D
Kaye
Joel
J
Langer
Noga
N
Bellomo
Stephen
S
Shavit
Moni
M
Pearlman
Andrew
A
Lippin
Yitzhak
Y
Panet
Amos
A
Shani
Noam
N
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D020405:Dermis / Q000378:metabolism / Q000637:transplantation*; D004921:Erythropoietin / Q000378:metabolism* / Q000627:therapeutic use*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D011994:Recombinant Proteins; D014161:Transduction, Genetic / Q000379:methods*; D014182:Transplantation, Autologous
D011994:Recombinant Proteins; D004921:Erythropoietin