DNA nanomapping using CRISPR-Cas9 as a programmable nanoparticle

被引:25
作者
Mikheikin, Andrey [1 ]
Olsen, Anita [1 ]
Leslie, Kevin [1 ]
Russell-Pavier, Freddie [2 ,3 ]
Yacoot, Andrew [2 ]
Picco, Loren [3 ]
Payton, Oliver [3 ]
Toor, Amir [4 ,5 ]
Chesney, Alden [5 ,6 ]
Gimzewski, James K. [7 ]
Mishra, Bud [8 ,9 ]
Reed, Jason [1 ,5 ]
机构
[1] Virginia Commonwealth Univ, Dept Phys, Richmond, VA 23284 USA
[2] Natl Phys Lab, Hampton Rd, Teddington TW11 0LW, Middx, England
[3] Interface Anal Ctr, HH Wills Phys Lab, Tyndall Ave, Bristol BS8 1TL, Avon, England
[4] VCU Sch Med, Dept Internal Med, Richmond, VA 23284 USA
[5] VCU Massey Canc Ctr, Richmond, VA 23284 USA
[6] VCU Sch Med, Dept Pathol, Richmond, VA 23284 USA
[7] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA
[8] NYU, Courant Inst Math Sci, Dept Comp Sci, New York, NY 10012 USA
[9] NYU, Courant Inst Math Sci, Dept Math, New York, NY 10012 USA
来源
NATURE COMMUNICATIONS | 2017年 / 8卷
基金
英国工程与自然科学研究理事会; 美国国家卫生研究院;
关键词
ATOMIC-FORCE MICROSCOPY; FOLLICULAR LYMPHOMA; GENOMIC DNA; BRCA1; MICA; BREAST; CANCER; GRADE; GENE; PCR;
D O I
10.1038/s41467-017-01891-9
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Progress in whole-genome sequencing using short-read (e.g., <150 bp), next-generation sequencing technologies has reinvigorated interest in high-resolution physical mapping to fill technical gaps that are not well addressed by sequencing. Here, we report two technical advances in DNA nanotechnology and single-molecule genomics: (1) we describe a labeling technique (CRISPR-Cas9 nanoparticles) for high-speed AFM-based physical mapping of DNA and (2) the first successful demonstration of using DVD optics to image DNA molecules with high-speed AFM. As a proof of principle, we used this new "nanomapping" method to detect and map precisely BCL2-IGH translocations present in lymph node biopsies of follicular lymphoma patents. This HS-AFM "nanomapping" technique can be complementary to both sequencing and other physical mapping approaches.
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页数:9
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