7月10日,，P NATL ACAD SCI USA雜志報道了一項通過表達單鏈抗體阻斷惡性瘧原蟲孢子在蚊蟲體內(nèi)產(chǎn)生的研究。這為惡性瘧疾防治的研究開辟了一條新路,。
在給予惡性瘧原蟲時,，表達m1C3, m4B7，或m2A10單鏈抗體（scFvs）的斯氏按蚊（Anopheles stephensic）與對照組相比,，感染水平顯著較低,。
這些scFvs源于分別特異性針對寄生蟲殼多糖酶：25 kDa蛋白和環(huán)子蛋白所產(chǎn)生的抗體,。利用位點特異性重組，合成m2A10與m1C3或m4B7組合抗體的轉基因序列被插入先前研究過的蚊子染色體的"?？?quot;位點,。
研究者在四個不同的基因組位置檢測了這些轉基因的表達水平，并對一個允許這些轉基因發(fā)生組織和性別特異性表達的?？空军c,，進一步加以研究。結果僅發(fā)現(xiàn)一個顯著的健康性效應：在染色體?？课稽c帶有轉基因的成體雄性斯氏按蚊顯示出遲發(fā)性生存率的降低,。
在四分之三的實驗中，給予帶有m4B7/m2A10的蚊子惡性瘧原蟲,，很少或根本沒有瘧原蟲孢子（感染人類的寄生蟲階段）的產(chǎn)生,。在發(fā)育相關時間段誘導m1C3/m2A10同時表達，則無法在施加了惡性瘧原蟲的m4B7/m2A10蚊子體內(nèi)檢測到瘧原蟲孢子,。
這些研究支持的結論是,，一個單拷貝的雙抗體基因的表達可以完全抑制瘧原蟲的發(fā)展，而不損害蚊子的存活,。這為惡性瘧疾的防治提供了新的思路,。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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PMID:
Transgenic Anopheles stephensi coexpressing single-chain antibodies resist Plasmodium falciparum development
Alison T. Isaacsa,b,Nijole Jasinskieneb,Mikhail Tretiakovb,Isabelle Thieryc,Agnès Zettorc,Catherine Bourgouinc,d, andAnthony A. Jamesa,b,1
Anopheles stephensi mosquitoes expressing m1C3, m4B7, or m2A10 single-chain antibodies (scFvs) have significantly lower levels of infection compared to controls when challenged with Plasmodium falciparum, a human malaria pathogen. These scFvs are derived from antibodies specific to a parasite chitinase, the 25 kDa protein and the circumsporozoite protein, respectively. Transgenes comprising m2A10 in combination with either m1C3 or m4B7 were inserted into previously-characterized mosquito chromosomal “docking” sites using site-specific recombination. Transgene expression was evaluated at four different genomic locations and a docking site that permitted tissue- and sex-specific expression was researched further. Fitness studies of docking site and dual scFv transgene strains detected only one significant fitness cost: adult docking-site males displayed a late-onset reduction in survival. The m4B7/m2A10 mosquitoes challenged with P. falciparum had few or no sporozoites, the parasite stage infective to humans, in three of four experiments. No sporozoites were detected in m1C3/m2A10 mosquitoes in challenge experiments when both genes were induced at developmentally relevant times. These studies support the conclusion that expression of a single copy of a dual scFv transgene can completely inhibit parasite development without imposing a fitness cost on the mosquito.
