Inverted mirror image molecular beacon-based three concatenated logic gates to detect p53 tumor suppressor gene

Copyright © 2018 Elsevier B.V. All rights reserved..

Mutation of p53 tumor suppressor gene represents one of the early molecular events in tumor initiation and progression. Although molecular computing holds tremendous potential with important applications in diagnosis, prognosis and treatment of human diseases at the molecular level, designing molecular logic gates to implement cascade amplification via operating autonomously for the detection of point mutations still remains challenging. In this contribution, we developed a three concatenated logic gates (TCLG) to perform multiple strand displacement amplification (m-SDA) for screening the cancer-related point mutations only via designing an innovative molecular beacon (MB). Specifically, using p53 gene as model target, extending the two ends of a MB via adding two fragments with the same sequence achieves two unique terminal single-stranded (ss) overhangs. After self-folding of MB into hairpin structure, the two overhangs exhibit a near inverted mirror image (IM) relationship if taking the base nature and direction into account. For this, the probe is called IM-MB. Because cascade SDAs can occur on IM-MB and promote each other, the target gene can be detected down to 10 pM. Along this line, the TCLG circuit was proposed, and two primers and target gene serve as the indispensable input signals. Utilizing this logic circuit, the point mutation or absence of target gene can be sensitively screened. Moreover, its potential application in the recognition of point mutations in complex biomatrix has been demonstrated via blind test. The proof-of-concept scheme is expected to provide new insight into the development of DNA-based molecular logic gates and their applications in basic research, medical diagnosis and precise treatment and treatment of genetic diseases.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:1051

Enthalten in:

Analytica chimica acta - 1051(2019) vom: 21. März, Seite 179-186

Sprache:

Englisch

Beteiligte Personen:

Xue, Chang [VerfasserIn]
Xiao, Shuai [VerfasserIn]
Ouyang, Chang-He [VerfasserIn]
Li, Cong-Cong [VerfasserIn]
Gao, Zhi-Hua [VerfasserIn]
Shen, Zhi-Fa [VerfasserIn]
Wu, Zai-Sheng [VerfasserIn]

Links:

Volltext

Themen:

DNA
DNA Primers
Journal Article
Logic gates
Multiple strand displacement amplification
Oligonucleotide Probes
P53 tumor suppressor gene
Tumor Suppressor Protein p53

Anmerkungen:

Date Completed 03.04.2019

Date Revised 03.04.2019

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.aca.2018.11.029

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM292893442