用激光發(fā)射裝置標(biāo)記敵方目標(biāo),，引導(dǎo)戰(zhàn)斗機(jī)或轟炸機(jī)對其實(shí)施精確打擊,。這是在好萊塢大片中經(jīng)常可以看到的場景,，同時(shí)也是現(xiàn)代戰(zhàn)爭中地空協(xié)作的一個(gè)經(jīng)典范例,。而日前由美國南加州大學(xué)研究人員完成的一項(xiàng)研究，有望讓這一戰(zhàn)術(shù)在人類與艾滋病的戰(zhàn)斗中獲得應(yīng)用,，實(shí)現(xiàn)對艾滋病病毒（HIV）的精確打擊,。
據(jù)美國每日科學(xué)網(wǎng)8月9日（北京時(shí)間）報(bào)道，南加州大學(xué)的研究人員日前培育出了一種病毒,，其能夠作為載體精確定位被HIV病毒感染的細(xì)胞,。這無疑為艾滋病這個(gè)“超級癌癥”的治療帶來了無限遐想，相關(guān)治療方法也有望因此獲得新突破,。
負(fù)責(zé)該項(xiàng)研究的南加州大學(xué)維特比工程學(xué)院教授王品（音譯）說,，由他們培育出的這種慢病毒載體能夠定位被HIV病毒感染的細(xì)胞，而后可采用“自殺基因療法”,，讓后續(xù)藥物發(fā)現(xiàn)并將病毒細(xì)胞摧毀,。這個(gè)過程類似于軍事上的“友軍激光標(biāo)記”——即地面戰(zhàn)斗人員使用激光發(fā)射裝置對敵方目標(biāo)進(jìn)行標(biāo)記，而后戰(zhàn)斗機(jī)在激光的引導(dǎo)下對目標(biāo)實(shí)施精確打擊,。這種針對艾滋病病毒的慢病毒載體將只對那些被艾滋病病毒感染的細(xì)胞進(jìn)行標(biāo)記,，未被感染的細(xì)胞則將完全處于不會受到傷害的“安全區(qū)域”，這就避免了治療所帶來的副作用,。
“就目前而言,，在單獨(dú)使用的情況下，還沒有任何藥物能夠?qū)崿F(xiàn)如此‘精確的打擊’,。如果你能夠消滅掉所有被HIV病毒感染的細(xì)胞,，將最終能夠找到解決問題的辦法。”王品說,。
研究人員介紹說,，目前這種慢病毒載體只在培養(yǎng)皿中進(jìn)行過測試。實(shí)驗(yàn)顯示,，該法單次能夠殺滅35%的艾滋病病毒,。雖然這一比例并不算高，但在應(yīng)用于臨床時(shí),，可將其反復(fù)使用數(shù)次,，以達(dá)到最佳療效。在接下來的步驟中,，研究人員將使用這種方法進(jìn)行小鼠實(shí)驗(yàn),。
王品說，雖然這是一個(gè)重大的突破,，為艾滋病的治療指明了一條新的路徑,，但目前這項(xiàng)研究尚處于初級階段，距離治愈艾滋病還有很長的一段路要走。
該項(xiàng)目由美國國立衛(wèi)生研究院（NIH）資助,，相關(guān)論文發(fā)表在7月23日出版的《病毒研究》雜志上,。（生物谷Bioon.com）
DOI:10.1016/j.virusres.2011.07.010
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Engineered lentiviral vectors pseudotyped with a CD4 receptor and a fusogenic protein can target cells expressing HIV-1 envelope proteins
Chi-Lin Lee, Jason Dang, Kye-Il Joo and Pin Wang
Lentiviral vectors (LVs) derived from human immunodeficiency virus type 1 (HIV-1) are promising vehicles for gene delivery because they not only efficiently transduce both dividing and non-dividing cells, but also maintain long-term transgene expression. Development of an LV system capable of transducing cells in a cell type-specific manner can be beneficial for certain applications that rely on targeted gene delivery. Previously it was shown that an inverse fusion strategy that incorporated an HIV-1 receptor (CD4) and its co-receptor (CXCR4 or CCR5) onto vector surfaces could confer to LVs the ability to selectively deliver genes to HIV-1 envelope-expressing cells. To build upon this work, we aim to improve its relatively low transduction efficiency and circumvent its inability to target multiple tropisms of HIV-1 by a single vector. We investigated a method to create LVs co-enveloped with the HIV-1 cellular receptor CD4 and a fusogenic protein derived from the Sindbis virus glycoprotein and tested its efficiency to selectively deliver genes into cells expressing HIV-1 envelope proteins. The engineered LV system yields a higher level of transduction efficiency and a broader tropism towards cells displaying the HIV-1 envelope protein (Env) than the previously developed system. Furthermore, we demonstrated in vitro that this engineered LV can preferentially deliver suicide gene therapy to HIV-1 envelope-expressing cells. We conclude that it is potentially feasible to target LVs towards HIV-1-infected cells by functional co-incorporation of the CD4 and fusogenic proteins, and provide preliminary evidence for further investigation on a potential alternative treatment for eradicating HIV-1-infected cells that produce drug-resistant viruses after highly active antiretroviral therapy (HAART).
