7月10日，P NATL ACAD SCI USA杂志报道了一项通过表达单链抗体阻断恶性疟原虫孢子在蚊虫体内产生的研究。这为恶性疟疾防治的研究开辟了一条新路。
在给予恶性疟原虫时，表达m1C3, m4B7，或m2A10单链抗体（scFvs）的斯氏按蚊（Anopheles stephensic）与对照组相比，感染水平显著较低。
这些scFvs源于分别特异性针对寄生虫壳多糖酶：25 kDa蛋白和环子蛋白所产生的抗体。利用位点特异性重组，合成m2A10与m1C3或m4B7组合抗体的转基因序列被插入先前研究过的蚊子染色体的"停靠"位点。
研究者在四个不同的基因组位置检测了这些转基因的表达水平，并对一个允许这些转基因发生组织和性别特异性表达的停靠站点，进一步加以研究。结果仅发现一个显著的健康性效应：在染色体停靠位点带有转基因的成体雄性斯氏按蚊显示出迟发性生存率的降低。
在四分之三的实验中，给予带有m4B7/m2A10的蚊子恶性疟原虫，很少或根本没有疟原虫孢子（感染人类的寄生虫阶段）的产生。在发育相关时间段诱导m1C3/m2A10同时表达，则无法在施加了恶性疟原虫的m4B7/m2A10蚊子体内检测到疟原虫孢子。
这些研究支持的结论是，一个单拷贝的双抗体基因的表达可以完全抑制疟原虫的发展，而不损害蚊子的存活。这为恶性疟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.
