Constitutive and inducible co-expression systems for non-viral osteoinductive gene therapy
Transcriptional Activation
0301 basic medicine
Bone Morphogenetic Protein 7
Genetic Vectors
Osteocalcin
Bone Morphogenetic Protein 2
Diseases of the musculoskeletal system
Cell Line
Mice
03 medical and health sciences
Osteogenesis
Animals
Humans
Bone Morphogenetic Protein 7/genetics
Orthopedic surgery
0303 health sciences
Osteoblasts
Mesenchymal Stem Cells/cytology
Osteoblasts/cytology
Mesenchymal Stem Cells
Genetic Therapy
Bone Morphogenetic Protein 2/genetics
3. Good health
Genetic Vectors/genetics
RC925-935
Osteocalcin/genetics
RD701-811
DOI:
10.22203/ecm.v027a13
Publication Date:
2016-11-28T05:27:46Z
AUTHORS (8)
ABSTRACT
Tissue regenerative gene therapy requires expression strategies that deliver therapeutic effective amounts of transgenes.As physiological patterns are more complex than high-level a singular gene, we aimed at constitutive or inducible co-expression 2 transgenes simultaneously.Co-expression human bone morphogenetic protein and 7 (BMP2/7) from constitutively expressing doxycycline plasmids was evaluated in vitro C2C12 cells with osteocalcin reporter assays standard for osteogenic differentiation.The systems were additionally tested an vivo pilot ectopic formation after repeated naked DNA injection to murine muscle tissue.Inductor controlled differentiation demonstrated co-expression.Both systems, constitutive, achieved significantly better single factor expression.The potency the dependent on relative cassette topology.In vivo, 6/13 animals (46 % efficacy) days 14 28 hind limb muscles as proven by µCT histological evaluation.In findings devised vector BMP2/7 strategy mediates superior osteoinduction, can be applied inductor fashion its efficiency is results indicate non-viral transfer effectively without application biomaterials, recombinant growth factors, offering promising alternative current treatment potential clinical translation future.
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