title: Transcript-activated collagen matrix as sustained mRNA delivery system for bone regeneration.
abstract: Transcript therapies using chemically modified messenger RNAs (cmRNAs) are emerging as safe and promising alternatives for gene and recombinant protein therapies. However, their applications have been limited due to transient translation and relatively low stability of cmRNAs compared to DNA. Here we show that vacuum-dried cmRNA-loaded collagen sponges, termed transcript activated matrices (TAMs), can serve as depots for sustained delivery of cmRNA. TAMs provide steady state protein production for up to six days, and substantial residual expression until 11days post transfection. Another advantage of this technology was nearly 100% transfection efficiency as well as low toxicity in vitro. TAMs were stable for at least 6months at room temperature. Human BMP-2-encoding TAMs induced osteogenic differentiation of MC3T3-E1 cells in vitro and bone regeneration in a non-critical rat femoral bone defect model in vivo. In summary, TAMs are a promising tool for bone regeneration and potentially also for other applications in regenerative medicine and tissue engineering.
authors: Institute of Molecular Immunology - Experimental Oncology, Technische Universität München, Munich, Germany.
authors: Zohreh Sadat
authors: ZS
authors: Badieyan
authors: Institute of Molecular Immunology - Experimental Oncology, Technische Universität München, Munich, Germany; Ethris GmbH, Planegg, Germany.
authors: Taras
authors: T
authors: Berezhanskyy
authors: Ethris GmbH, Planegg, Germany; Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Maximilian
authors: M
authors: Utzinger
authors: Ethris GmbH, Planegg, Germany.
authors: Manish Kumar
authors: MK
authors: Aneja
authors: Ethris GmbH, Planegg, Germany.
authors: Daniela
authors: D
authors: Emrich
authors: Department of Physiology, Pathophysiology and Experimental Endocrinology, Veterinärmedizinische Universität Wien, Vienna, Austria.
authors: Reinhold
authors: R
authors: Erben
authors: Department of Physiology, Pathophysiology and Experimental Endocrinology, Veterinärmedizinische Universität Wien, Vienna, Austria.
authors: Christiane
authors: C
authors: Schüler
authors: Center for Nanoscience and Department of Physics, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Philipp
authors: P
authors: Altpeter
authors: Ethris GmbH, Planegg, Germany.
authors: Mehrije
authors: M
authors: Ferizi
authors: Ethris GmbH, Planegg, Germany.
authors: Günther
authors: G
authors: Hasenpusch
authors: Ethris GmbH, Planegg, Germany.
authors: Carsten
authors: C
authors: Rudolph
authors: Institute of Molecular Immunology - Experimental Oncology, Technische Universität München, Munich, Germany; Ethris GmbH, Planegg, Germany. Electronic address: plank@lrz.tum.de.
authors: Christian
authors: C
authors: Plank
mesh_terms: D000072283:A549 Cells; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003692:Delayed-Action Preparations; D012333:RNA, Messenger; D003094:Collagen
keywords: Bone regeneration; Chemically modified mRNA (cmRNA); Human bone morphogenetic protein 2 (hBMP-2); Sustained delivery; Transcript therapy; Transcript-activated matrix (TAM)