伦敦帝国理工学院George K. Christophides小组的最新研究揭示了坦桑尼亚具有基因驱动能力的蚊子抑制了患者源性疟疾。相关论文发表在2025年12月10日出版的《自然》杂志上。

该课题组研究人员之前已经证明，修饰冈比亚按蚊表达两种外源抗菌肽可以抑制实验室培养的恶性疟原虫的孢子发育，模型预测，当与基因驱动相结合时，将对非洲的疟疾消除做出重大贡献。

然而，这种修饰对遗传多样性的、自然传播的寄生虫分离株的有效性仍然未知。为了解决这一重大差距，该课题组研究人员在坦桑尼亚建立了基础设施和研究能力，使他们的技术适应非洲的情况，使当地冈比亚疟的工程得以控制。

在这里，研究组报道了一种转基因菌株的产生，该菌株具有非自主基因驱动能力，可以有效抑制从自然感染儿童中获得的遗传多样性恶性疟原虫分离株。当补充另一个局部工程菌株提供的Cas9内切酶时，这些遗传修饰有效地遗传给后代。他们的工作使基因驱动技术向应用迈出了关键的一步，通过在野生蚊子种群中有针对性地传播有益的遗传性状，为消灭疟疾提供了一种适合当地的强大工具。

据了解，基因驱动技术通过将基因改造引入野生蚊子种群以降低其媒介能力，为抗击疟疾提供了一种变革性的方法。虽然已经开发出有效的修改方法，但这些努力仅限于全球北方的实验室。

附：英文原文

Title: Gene-drive-capable mosquitoes suppress patient-derived malaria in Tanzania

Author: Habtewold, Tibebu, Lwetoijera, Dickson Wilson, Hoermann, Astrid, Mashauri, Rajabu, Matwewe, Fatuma, Mwanga, Rehema, Kweyamba, Prisca, Maganga, Gilbert, Magani, Beatrice Philip, Mtama, Rachel, Mahonje, Moze Ally, Tambwe, Mgeni Mohamed, Tarimo, Felista, Chennuri, Pratima R., Cai, Julia A., Del Corsano, Giuseppe, Capriotti, Paolo, Sasse, Peter, Moore, Jason, Hudson, Douglas, Manjurano, Alphaxard, Tarimo, Brian, Vlachou, Dina, Moore, Sarah, Windbichler, Nikolai, Christophides, George K.

Issue&Volume: 2025-12-10

Abstract: Gene drive technology presents a transformative approach to combatting malaria by introducing genetic modifications into wild mosquito populations to reduce their vectorial capacity. Although effective modifications have been developed, these efforts have been confined to laboratories in the global north. We previously demonstrated that modifying Anopheles gambiae to express two exogenous antimicrobial peptides inhibits the sporogonic development of laboratory-cultured Plasmodium falciparum, with models predicting substantial contributions to malaria elimination in Africa when integrated with gene drive1,2,3. However, the effectiveness of this modification against genetically diverse, naturally circulating parasite isolates remained unknown. To address this critical gap, we adapted our technology for an African context by establishing infrastructural and research capacity in Tanzania, enabling the engineering of local A. gambiae under containment. Here we report the generation of a transgenic strain equipped with non-autonomous gene drive capabilities that robustly inhibits genetically diverse P. falciparum isolates obtained from naturally infected children. These genetic modifications were efficiently inherited by progeny when supplemented with Cas9 endonuclease provided by another locally engineered strain. Our work brings gene drive technology a critical step closer to application, providing a locally tailored and powerful tool for malaria eradication through the targeted dissemination of beneficial genetic traits in wild mosquito populations.

DOI: 10.1038/s41586-025-09685-6

Source: https://www.nature.com/articles/s41586-025-09685-6