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HIV治療薬の細胞内への搬送にナノチューブを利用 Batten Down The Hatches Against HIV
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Batten Down The Hatches Against HIV
Main Category: HIV / AIDS News
Article Date: 26 Feb 2007 - 6:00 PST
HIV治療薬の細胞内への搬送にナノチューブを利用
遺伝子治療の有望な方法について、小さなDNAの断片(iRNA)がある。これは特定の遺伝子と結びつき、それに対応する病気に関連するタンパク質の"転換translation"を阻止する。
これまでその障害は、細胞へのRNAの効率的かつ対象を特定した搬送であった。
Stanford University大学の研究グループはカーボンナノチューブを”搬送手段”として選択した。
これにより、遺伝子群の機能を停止させる(switch off)RNAの断片を人間のT細胞内と主要な血球内に侵入させることに成功した。これらの遺伝子は細胞表面のHIVに特化したレセプター及びco-receptorsに対応する。
T-cell内に侵入するため、ビールスはまず，CD4 というリセプターとドッキングしなければならない。
同時に関与するのがco-receptorのCXCR4である。
短いiRNAの鎖を使って、T-cellのCD4 とCXCR4遺伝子が機能停止される。
この時点で、T-cellはこれらのレセプター生産を停止し、その結果、ビールスは細胞表面に攻撃地点を発見不能となる。
これにより、HIV感染のスピードは大幅に低下するが、これは既に研究で明らかになっている。
しかし、どのようにしてRNAの断片をT-cell内に搬送するか？
この研究では細胞膜の素材もこれと同じ分子であるリン脂質をポリエチレングリコールの鎖に取り付けた。
リン脂質はカーボンナノチューブの外壁にしっかり取り付いて、一方、ポリエチレングリコール鎖はその周りの溶液に突出する。
必要なRNA分子はこれらの鎖の末端にきちんと接着されている。
Carbon nanotubes transport gene therapy drug into T-cells known to block HIV from entering cells in vitro
A promising approach to gene therapy involves short DNA fragments (interfering RNA) that bind to specific genes and block their "translation" into the corresponding, disease-related protein.
A stumbling block has been the efficient and targeted delivery of RNA into the cells.
Researchers led by Hongjie Dai at Stanford University have chosen to use carbon nanotubes as their "means of transport".
This has allowed them to successfully introduce RNA fragments that "switch off" the genes for special HIV-specific receptors and co-receptors on the cells' surface into human T-cells and primary blood cells. This leaves few "entry hatches" for the HIV viruses. The researchers report in the journal Angewandte Chemie that this allows for much better silencing effect to the cells than current transport systems based on liposomes.
T-cells are one of the types of white blood cells important for a good immune defense; they detect and destroy virus-affected cells. However, they themselves are among the targets attacked by HIV.
In order to enter into a T-cell, the virus must first dock to a receptor known as CD4.
Also involved is the co-receptor CXCR4.
The use of short interfering RNA strands allows the CD4 and CXCR4 genes of the T-cell to be shut off.
The T-cell then strops producing these receptors and the virus cannot find any points of attack on the surface of the cell.
This could significantly slow down an HIV infection, as previous work have shown.
But how to get the RNA fragments into the T-cells? The shells of nonpathogenic viruses can be used to smuggle genetic material into cells, but this is dangerous in therapeutic applications because they can trigger allergies. Liposomes, tiny bubbles of fat, are safe but have proven to be ineffective for use in T-cells. Dai and his co-workers have tested a new transport system: carbon nanotubes are known for their abilities to be absorbed by cells and to smuggle other molecules in at the same time.
The researchers attached phospholipids - molecules from which cell membranes are also made - to chains of polyethylene glycol.
The phospholipids nestle securely onto the outer wall of the carbon nanotubes while the polyethylene glycol chains protrude into the surrounding solution.
The required RNA molecules were fastened to the ends of these chains. Once inside the cell, the RNA could easily be split off by means of a sulfur-sulfur bridge.
Batten Down The Hatches Against HIV
Main Category: HIV / AIDS News
Article Date: 26 Feb 2007 - 6:00 PST
HIV治療薬の細胞内への搬送にナノチューブを利用
遺伝子治療の有望な方法について、小さなDNAの断片(iRNA)がある。これは特定の遺伝子と結びつき、それに対応する病気に関連するタンパク質の"転換translation"を阻止する。
これまでその障害は、細胞へのRNAの効率的かつ対象を特定した搬送であった。
Stanford University大学の研究グループはカーボンナノチューブを”搬送手段”として選択した。
これにより、遺伝子群の機能を停止させる(switch off)RNAの断片を人間のT細胞内と主要な血球内に侵入させることに成功した。これらの遺伝子は細胞表面のHIVに特化したレセプター及びco-receptorsに対応する。
T-cell内に侵入するため、ビールスはまず，CD4 というリセプターとドッキングしなければならない。
同時に関与するのがco-receptorのCXCR4である。
短いiRNAの鎖を使って、T-cellのCD4 とCXCR4遺伝子が機能停止される。
この時点で、T-cellはこれらのレセプター生産を停止し、その結果、ビールスは細胞表面に攻撃地点を発見不能となる。
これにより、HIV感染のスピードは大幅に低下するが、これは既に研究で明らかになっている。
しかし、どのようにしてRNAの断片をT-cell内に搬送するか？
この研究では細胞膜の素材もこれと同じ分子であるリン脂質をポリエチレングリコールの鎖に取り付けた。
リン脂質はカーボンナノチューブの外壁にしっかり取り付いて、一方、ポリエチレングリコール鎖はその周りの溶液に突出する。
必要なRNA分子はこれらの鎖の末端にきちんと接着されている。
Carbon nanotubes transport gene therapy drug into T-cells known to block HIV from entering cells in vitro
A promising approach to gene therapy involves short DNA fragments (interfering RNA) that bind to specific genes and block their "translation" into the corresponding, disease-related protein.
A stumbling block has been the efficient and targeted delivery of RNA into the cells.
Researchers led by Hongjie Dai at Stanford University have chosen to use carbon nanotubes as their "means of transport".
This has allowed them to successfully introduce RNA fragments that "switch off" the genes for special HIV-specific receptors and co-receptors on the cells' surface into human T-cells and primary blood cells. This leaves few "entry hatches" for the HIV viruses. The researchers report in the journal Angewandte Chemie that this allows for much better silencing effect to the cells than current transport systems based on liposomes.
T-cells are one of the types of white blood cells important for a good immune defense; they detect and destroy virus-affected cells. However, they themselves are among the targets attacked by HIV.
In order to enter into a T-cell, the virus must first dock to a receptor known as CD4.
Also involved is the co-receptor CXCR4.
The use of short interfering RNA strands allows the CD4 and CXCR4 genes of the T-cell to be shut off.
The T-cell then strops producing these receptors and the virus cannot find any points of attack on the surface of the cell.
This could significantly slow down an HIV infection, as previous work have shown.
But how to get the RNA fragments into the T-cells? The shells of nonpathogenic viruses can be used to smuggle genetic material into cells, but this is dangerous in therapeutic applications because they can trigger allergies. Liposomes, tiny bubbles of fat, are safe but have proven to be ineffective for use in T-cells. Dai and his co-workers have tested a new transport system: carbon nanotubes are known for their abilities to be absorbed by cells and to smuggle other molecules in at the same time.
The researchers attached phospholipids - molecules from which cell membranes are also made - to chains of polyethylene glycol.
The phospholipids nestle securely onto the outer wall of the carbon nanotubes while the polyethylene glycol chains protrude into the surrounding solution.
The required RNA molecules were fastened to the ends of these chains. Once inside the cell, the RNA could easily be split off by means of a sulfur-sulfur bridge.
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, Mar 12 2007, 6:29 AM EDT
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