Third-generation rabies viral vectors allow nontoxic retrograde targeting of projection neurons with greatly increased efficiency.
Third-generation rabies viral vectors allow nontoxic retrograde targeting of projection neurons with greatly increased efficiency.
复制标题
第三代狂犬病病毒载体允许无毒逆行靶向投射神经元，效率大大提高。
DOI：
10.1016/j.crmeth.2023.100644
复制
发表时间：
2023-11-20
期刊：
影响因子：
--
通讯作者：
Wickersham IR
中科院分区：
文献类型：
--
作者：
Jin L;Sullivan HA;Zhu M;Lea NE;Lavin TK;Fu X;Matsuyama M;Hou Y;Feng G;Wickersham IR
狂犬病病毒载体已成为系统神经科学工具包的重要组成部分，允许直接逆行靶向投射神经元和单突触追踪输入到定义的突触后群体，但第一代（ΔG）载体的快速细胞毒性限制了它们在短期实验中的使用。我们最近引入了第二代双缺失突变（ΔGL）狂犬病病毒载体，表明它们有效地逆行感染投射神经元并有效表达重组酶，但几乎没有可检测到的毒性;最近，我们已经证明ΔGL病毒可用于单突触追踪，其细胞毒性远低于第一代系统。在这里，我们介绍了第三代（ΔL）狂犬病病毒载体，它似乎与第二代一样无毒，但具有生长到更高滴度的主要优势，导致体内逆行标记神经元的数量显着增加。第三代（ΔL）狂犬病毒载体只有一个基因从其基因组中缺失Δ L载体对标记细胞无毒ΔL载体在体内标记的神经元比以前的无毒狂犬病毒载体多得多狂犬病毒载体是标记投射神经元的有用工具，但第一代载体具有细胞毒性，第二代载体难以在高浓度下生产，这就限制了标记神经元的数量。在这里，我们介绍了第三代载体，既无毒又容易生长到高浓度，允许在体内标记更多的神经元。狂犬病病毒载体是标记投射神经元的有用工具，但第一代载体具有细胞毒性，第二代载体难以生产。Jin等人引入第三代载体，既无毒又容易生长到高浓度，允许在体内标记更多的神经元。
Rabies viral vectors have become important components of the systems neuroscience toolkit, allowing both direct retrograde targeting of projection neurons and monosynaptic tracing of inputs to defined postsynaptic populations, but the rapid cytotoxicity of first-generation (ΔG) vectors limits their use to short-term experiments. We recently introduced second-generation, double-deletion-mutant (ΔGL) rabies viral vectors, showing that they efficiently retrogradely infect projection neurons and express recombinases effectively but with little to no detectable toxicity; more recently, we have shown that ΔGL viruses can be used for monosynaptic tracing with far lower cytotoxicity than the first-generation system. Here, we introduce third-generation (ΔL) rabies viral vectors, which appear to be as nontoxic as second-generation ones but have the major advantage of growing to much higher titers, resulting in significantly increased numbers of retrogradely labeled neurons in vivo. Third-generation (ΔL) rabies viral vectors have only one gene deleted from their genomes ΔL vectors are nontoxic to labeled cells ΔL vectors label many more neurons in vivo than do previous nontoxic rabies viral vectors Rabies viral vectors are useful tools for labeling projection neurons, but first-generation vectors are cytotoxic, and second-generation vectors are difficult to produce at high concentrations, and this limits the numbers of labeled neurons. Here, we introduce third-generation vectors that are both nontoxic and easily grown to high concentrations, allowing labeling of many more neurons in vivo. Rabies viral vectors are useful tools for labeling projection neurons, but first-generation vectors are cytotoxic, and second-generation vectors are difficult to produce. Jin et al. introduce third-generation vectors that are both nontoxic and easily grown to high concentrations, allowing labeling of many more neurons in vivo.
登录
查看更多内容
小鼠皮质-基底节-丘脑网络。
影响因子：
64.8
作者：
Foster NN;Barry J;Korobkova L;Garcia L;Gao L;Becerra M;Sherafat Y;Peng B;Li X;Choi JH;Gou L;Zingg B;Azam S;Lo D;Khanjani N;Zhang B;Stanis J;Bowman I;Cotter K;Cao C;Yamashita S;Tugangui A;Li A;Jiang T;Jia X;Feng Z;Aquino S;Mun HS;Zhu M;Santarelli A;Benavidez NL;Song M;Dan G;Fayzullina M;Ustrell S;Boesen T;Johnson DL;Xu H;Bienkowski MS;Yang XW;Gong H;Levine MS;Wickersham I;Luo Q;Hahn JD;Lim BK;Zhang LI;Cepeda C;Hintiryan H;Dong HW
通讯作者：
Dong HW
负链RNA病毒的聚合酶。
影响因子：
5.9
作者：
Morin, Benjamin;Kranzusch, Philip J.;Rahmeh, Amal A.;Whelan, Sean P. J.
通讯作者：
Whelan, Sean P. J.
影响因子：
3.4
作者：
Faulkner, Regina L.;Wall, Nicholas R.;Cline, Hollis T.
通讯作者：
Cline, Hollis T.
影响因子：
5.4
作者：
Gomme, Emily A.;Faul, Elizabeth J.;Schnell, Matthias J.
通讯作者：
Schnell, Matthias J.
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H