Cut and Paste for Cancer Treatment: A DNA Nanodevice that Cuts Out an RNA Marker Sequence to Activate a Therapeutic Function

被引:17
作者
Molden, Tatiana A. [1 ]
Niccum, Caitlyn T. [1 ]
Kolpashchikov, Dmitry M. [1 ]
机构
[1] Univ Cent Florida, Chem Dept, Orlando, FL 32816 USA
关键词
deoxyribozymes; DNA nanotechnology; gene therapy; KRAS gene; split probes; MESSENGER-RNA; K-RAS; MACHINE; CELL;
D O I
10.1002/anie.202006384
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
DNA nanotechnology uses oligonucleotide strands to assemble molecular structures capable of performing useful operations. Here, we assembled a multifunctional prototype DNA nanodevice, DOCTR, that recognizes a single nucleotide mutation in a cancer marker RNA. The nanodevice then cuts out a signature sequence and uses it as an activator for a "therapeutic" function, namely, the cleavage of another RNA sequence. The proposed design is a prototype for a gene therapy DNA machine that cleaves a housekeeping gene only in the presence of a cancer-causing point mutation and suppresses cancer cells exclusively with minimal side effects to normal cells.
引用
收藏
页码:21190 / 21194
页数:5
相关论文
共 29 条
[1]   The Future of Molecular Machines [J].
Aprahamian, Ivan .
ACS CENTRAL SCIENCE, 2020, 6 (03) :347-358
[2]   Programmable and autonomous computing machine made of biomolecules [J].
Benenson, Y ;
Paz-Elizur, T ;
Adar, R ;
Keinan, E ;
Livneh, Z ;
Shapiro, E .
NATURE, 2001, 414 (6862) :430-434
[3]   Allosteric hammerhead ribozyme TRAPs [J].
Burke, DH ;
Ozerova, NDS ;
Nilsen-Hamilton, M .
BIOCHEMISTRY, 2002, 41 (21) :6588-6594
[4]   Structure and functions of the 20S and 26S proteasomes [J].
Coux, O ;
Tanaka, K ;
Goldberg, AL .
ANNUAL REVIEW OF BIOCHEMISTRY, 1996, 65 :801-847
[5]   DNA nanotechnology for nucleic acid analysis: multifunctional molecular DNA machine for RNA detection [J].
Cox, A. J. ;
Bengtson, H. N. ;
Rohde, K. H. ;
Kolpashchikov, D. M. .
CHEMICAL COMMUNICATIONS, 2016, 52 (99) :14318-14321
[6]   Inhibition of Human Papillomavirus Type 16 Infection Using an RNA Aptamer [J].
Gabriela Valencia-Resendiz, Diana ;
Palomino-Vizcaino, Giovanni ;
Virginia Tapia-Vieyra, Juana ;
Luisa Benitez-Hess, Maria ;
Gabriela Leija-Montoya, Ana ;
Marat Alvarez-Salas, Luis .
NUCLEIC ACID THERAPEUTICS, 2018, 28 (02) :97-105
[7]   RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients [J].
Golan, Talia ;
Khvalevsky, Elina Zorde ;
Hubert, Ayala ;
Gabai, Rachel Malka ;
Hen, Naama ;
Segal, Amiel ;
Domb, Abraham ;
Harari, Gil ;
Ben David, Eliel ;
Raskin, Stephen ;
Goldes, Yuri ;
Goldin, Eran ;
Eliakim, Rami ;
Lahav, Maor ;
Kopleman, Yael ;
Dancour, Alain ;
Shemi, Amotz ;
Galun, Eithan .
ONCOTARGET, 2015, 6 (27) :24560-24570
[8]   Fluorescence Resonance Energy Transfer-Based DNA Tetrahedron Nanotweezer for Highly Reliable Detection of Tumor-Related mRNA in Living Cells [J].
He, Lei ;
Lu, Dan-Qing ;
Liang, Hao ;
Xie, Sitao ;
Luo, Can ;
Hu, Miaomiao ;
Xu, Liujun ;
Zhang, Xiaobing ;
Tan, Weihong .
ACS NANO, 2017, 11 (04) :4060-4066
[9]   RAS isoforms and mutations in cancer at a glance [J].
Hobbs, G. Aaron ;
Der, Channing J. ;
Rossman, Kent L. .
JOURNAL OF CELL SCIENCE, 2016, 129 (07) :1287-1292
[10]   A binary deoxyribozyme for nucleic acid analysis [J].
Kolpashchikov, Dmitry M. .
CHEMBIOCHEM, 2007, 8 (17) :2039-2042