title: Biopump: Autologous skin-derived micro-organ genetically engineered to provide sustained continuous secretion of therapeutic proteins.
abstract: A novel approach for sustained production of therapeutic proteins is described, using genetic modification of intact autologous micro-organ tissue explants from the subject's own skin. The skin-derived micro-organ can be maintained viable ex vivo for extended periods and is transduced with a transgene encoding a desired therapeutic protein, resulting in protein-secreting micro-organ (biopump (BP)). The daily protein production from each BP is quantified, enabling drug dosing by subcutaneous implantation of the requisite number of BPs into the patient to provide continuous production to the circulation of a known amount of the therapeutic protein. Each implanted BP remains localized and is accessible, to enable removal or ablation if needed. Examples from preclinical and clinical studies are presented, including use of associated virus vector 1 and helper-dependent adenoviral vectors producing BPs to provide long-term sustained secretion of recombinant interferon-α and erythropoietin.
authors.affiliation: Department of Cell Biology, the Hebrew University of Jerusalem, Israel.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mitrani
authors.forename: Andrew
authors.initials: A
authors.lastname: Pearlman
authors.forename: Baruch
authors.initials: B
authors.lastname: Stern
authors.forename: Reem
authors.initials: R
authors.lastname: Miari
authors.forename: Haim
authors.initials: H
authors.lastname: Goltsman
authors.forename: Nikolai
authors.initials: N
authors.lastname: Kunicher
authors.forename: Amos
authors.initials: A
authors.lastname: Panet
mesh_terms: D000256:Adenoviridae; D000818:Animals; D004921:Erythropoietin / Q000096:biosynthesis / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics; D016086:Lentivirus; D012867:Skin / Q000378:metabolism*; D016038:Skin Transplantation; D046509:Tissue Culture Techniques; D014161:Transduction, Genetic
chemical_list: D016898:Interferon-alpha; D004921:Erythropoietin