Inhibition of Xenograft tumor growth by gold nanoparticle-DNA oligonucleotide conjugates-assisted delivery of BAX mRNA.
Use of non-biological agents for mRNA delivery into living systems in order to induce heterologous expression of functional proteins may provide more advantages than the use of DNA and/or biological vectors for delivery. However, the low efficiency of mRNA delivery into live animals, using non-biological systems, has hampered the use of mRNA as a therapeutic molecule. Here, we show that gold nanoparticle-DNA oligonucleotide (AuNP-DNA) conjugates can serve as universal vehicles for more efficient delivery of mRNA into human cells, as well as into xenograft tumors generated in mice. Injections of BAX mRNA loaded on AuNP-DNA conjugates into xenograft tumors resulted in highly efficient mRNA delivery. The delivered mRNA directed the efficient production of biologically functional BAX protein, a pro-apoptotic factor, consequently inhibiting tumor growth. These results demonstrate that mRNA delivery by AuNP-DNA conjugates can serve as a new platform for the development of safe and efficient gene therapy.
Department of Life Science, Chung-Ang University, Seoul, Republic of Korea.
Ji-Hyun
JH
Yeom
Sang-Mi
SM
Ryou
Miae
M
Won
Mira
M
Park
Jeehyeon
J
Bae
Kangseok
K
Lee
D000818:Animals; D002470:Cell Survival; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D015316:Genetic Therapy; D006046:Gold / Q000737:chemistry*; D064593:Heterografts; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009841:Oligonucleotides / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000517:prevention & control*; D051028:bcl-2-Associated X Protein / Q000235:genetics*
C494826:BAX protein, human; D009841:Oligonucleotides; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D006046:Gold; D004247:DNA