Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers.
Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers.
复制标题
使用mRNA纳米载体进行治疗性细胞酸酯的命中编程。
DOI：
10.1038/s41467-017-00505-8
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发表时间：
2017-08-30
影响因子：
16.6
通讯作者：
Stephan MT
中科院分区：
文献类型：
--
作者：
Moffett HF;Coon ME;Radtke S;Stephan SB;McKnight L;Lambert A;Stoddard BL;Kiem HP;Stephan MT
Therapies based on immune cells have been applied for diseases ranging from cancer to diabetes. However, the viral and electroporation methods used to create cytoreagents are complex and expensive. Consequently, we develop targeted mRNA nanocarriers that are simply mixed with cells to reprogram them via transient expression. Here, we describe three examples to establish that the approach is simple and generalizable. First, we demonstrate that nanocarriers delivering mRNA encoding a genome-editing agent can efficiently knock-out selected genes in anti-cancer T-cells. Second, we imprint a long-lived phenotype exhibiting improved antitumor activities into T-cells by transfecting them with mRNAs that encode a key transcription factor of memory formation. Third, we show how mRNA nanocarriers can program hematopoietic stem cells with improved self-renewal properties. The simplicity of the approach contrasts with the complex protocols currently used to program therapeutic cells, so our methods will likely facilitate manufacturing of cytoreagents. Current widely used viral and electroporation methods for creating therapeutic cell-based products are complex and expensive. Here, the authors develop targeted mRNA nanocarriers that can transiently program gene expression by simply mixing them with cells, to improve their therapeutic potential.
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影响因子：
32.4
作者：
Kim MV;Ouyang W;Liao W;Zhang MQ;Li MO
通讯作者：
Li MO
影响因子：
3.5
作者：
Cribbs AP;Kennedy A;Gregory B;Brennan FM
通讯作者：
Brennan FM
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M
影响因子：
2.3
作者：
Freitag J;Bates D;Boyd R;Shah K;Barnard A;Huguenin L;Tenen A
通讯作者：
Tenen A
DOI：
10.1038/nrc.2016.97
发表时间：
2016-08-23
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Fesnak AD;June CH;Levine BL
通讯作者：
Levine BL