Journal
BIOCONJUGATE CHEMISTRY
Volume 21, Issue 1, Pages 56-63Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bc900296z
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Funding
- NIH
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R56AI041404, R01AI043198, R01AI041404] Funding Source: NIH RePORTER
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Single-walled carbon nanotubes (SWNT) have unique electronic, mechanical, and structural properties as well as chemical stability that make them ideal nanomaterials for applications in materials science and medicine. Here, we report the design and creation of it novel strategy for functionalizing SWNT to systemically silence a target gene in mice by delivering siRNA at doses of <1 mg/kg. SWNT were functionalized with lipids and natural amino acid-based dendrimers (TOT) and complexed to siRNA. Our model Study of the silencing efficiency of the TOT-siRNA complex showed that, in mice injected at 0.96 mg/kg, an endogenous gene for apoliproprotein B (ApoB) was silenced in liver, plasma levels of ApoB decreased, and total plasma cholesterol decreased. TOT-siRNA treatment was nontoxic and did not induce an immune response. Most (80%) of the RNA trigger molecules assembled with TOT were cleared from the body 48 h after injection, suggesting that the nanotubes did not cause siRNA aggregation or inhibit biodegradation and drug clearance in vivo. These results provide the first evidence that nanotubes can be functionalized with lipids and amino acids to systemically deliver siRNA. This new technology not only can be used for systemic RNAi, but may also be used to deliver other drugs in vivo.
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