TY - JOUR
T1 - Transcript-activated collagen matrix as sustained mRNA delivery system for bone regeneration
AU - Badieyan, Zohreh Sadat
AU - Berezhanskyy, Taras
AU - Utzinger, Maximilian
AU - Aneja, Manish Kumar
AU - Emrich, Daniela
AU - Erben, Reinhold
AU - Schüler, Christiane
AU - Altpeter, Philipp
AU - Ferizi, Mehrije
AU - Hasenpusch, Günther
AU - Rudolph, Carsten
AU - Plank, Christian
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/10/10
Y1 - 2016/10/10
N2 - 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 11 days 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 6 months 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.
AB - 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 11 days 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 6 months 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.
KW - Bone regeneration
KW - Chemically modified mRNA (cmRNA)
KW - Human bone morphogenetic protein 2 (hBMP-2)
KW - Sustained delivery
KW - Transcript therapy
KW - Transcript-activated matrix (TAM)
UR - http://www.scopus.com/inward/record.url?scp=84984788004&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2016.08.037
DO - 10.1016/j.jconrel.2016.08.037
M3 - Article
C2 - 27586186
AN - SCOPUS:84984788004
SN - 0168-3659
VL - 239
SP - 137
EP - 148
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -
