Difference between revisions of "Team:Hong Kong HKU/Description"

(→‎Current progress)
(→‎Early diagnosis of cancer)
Line 5: Line 5:
 
===Early diagnosis of cancer===
 
===Early diagnosis of cancer===
 
<br>
 
<br>
−
Cancer has always been a devastating disease. In 2012, there are 14.1 million new cancer cases worldwide.<ref name="American Cancer Society">American Cancer Society. (2015). Global Cancer Facts & Figures. Retrieved from http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-044738.pdf</ref> Early diagnosis of cancer may help to reduce the mortality rate and extend the life expectancy of patients. For instance, in the U. K., nearly 90% of patients diagnosed with stage I lung cancer lived for more than a year while only 19% of patients diagnosed at stage IV do so.<ref name="Public Health England">Public Health England. (2014). National Cancer Intelligence Network Cancer survival in England by stage. Retrieved from http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/survival#ref-3 </ref> Early diagnosis of cancer is also believed to be vital for successful treatment and recovery.
+
Cancer has always been a devastating disease. In 2012, there were 14.1 million new cancer cases worldwide.<ref name="American Cancer Society">American Cancer Society. (2015). Global Cancer Facts & Figures. Retrieved from http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-044738.pdf</ref> Early diagnosis of cancer may help to reduce the mortality rate and extend the life expectancy of patients. For instance, in the U. K., nearly 90% of patients diagnosed with stage I lung cancer lived for more than a year while only 19% of patients diagnosed at stage IV do so.<ref name="Public Health England">Public Health England. (2014). National Cancer Intelligence Network Cancer survival in England by stage. Retrieved from http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/survival#ref-3 </ref> Early diagnosis of cancer is also believed to be vital for successful treatment and recovery.
  
 
Significant gene mutations may signal the possibility of developing cancers. Although recent research has diagnosed cancers by analyzing individual genetic mutation profiles<ref name="Pereira, B., Chin, S., Rueda, O. M., Vollan, H. M., Provenzano, E., Bardwell, H. A., Pugh, M., et al.">Pereira, B., Chin, S., Rueda, O. M., Vollan, H. M., Provenzano, E., Bardwell, H. A., Pugh, M., et al. (2016). The somatic mutation profiles of 2500 primary breast cancers refine their genomic landscapes. Nature Communications</ref>,<ref name="Pereira, B., Chin, S. F., Rueda, O. M., Vollan, H. K. M., Provenzano, E., Bardwell, H. A., ... & Tsui, D. W.">Pereira, B., Chin, S. F., Rueda, O. M., Vollan, H. K. M., Provenzano, E., Bardwell, H. A., ... & Tsui, D. W. (2016). The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nature communications, 7.</ref>, such diagnostic method takes up considerable amount of time to obtain accurate results. As conventional diagnostic methods involve complicated procedures, simple DNA nanostructures have been introduced to detect cancer biomarkers to facilitate diagnosis.
 
Significant gene mutations may signal the possibility of developing cancers. Although recent research has diagnosed cancers by analyzing individual genetic mutation profiles<ref name="Pereira, B., Chin, S., Rueda, O. M., Vollan, H. M., Provenzano, E., Bardwell, H. A., Pugh, M., et al.">Pereira, B., Chin, S., Rueda, O. M., Vollan, H. M., Provenzano, E., Bardwell, H. A., Pugh, M., et al. (2016). The somatic mutation profiles of 2500 primary breast cancers refine their genomic landscapes. Nature Communications</ref>,<ref name="Pereira, B., Chin, S. F., Rueda, O. M., Vollan, H. K. M., Provenzano, E., Bardwell, H. A., ... & Tsui, D. W.">Pereira, B., Chin, S. F., Rueda, O. M., Vollan, H. K. M., Provenzano, E., Bardwell, H. A., ... & Tsui, D. W. (2016). The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nature communications, 7.</ref>, such diagnostic method takes up considerable amount of time to obtain accurate results. As conventional diagnostic methods involve complicated procedures, simple DNA nanostructures have been introduced to detect cancer biomarkers to facilitate diagnosis.

Revision as of 18:41, 30 June 2016

MENU ▤


Inspiration


Early diagnosis of cancer


Cancer has always been a devastating disease. In 2012, there were 14.1 million new cancer cases worldwide.[1] Early diagnosis of cancer may help to reduce the mortality rate and extend the life expectancy of patients. For instance, in the U. K., nearly 90% of patients diagnosed with stage I lung cancer lived for more than a year while only 19% of patients diagnosed at stage IV do so.[2] Early diagnosis of cancer is also believed to be vital for successful treatment and recovery.

Significant gene mutations may signal the possibility of developing cancers. Although recent research has diagnosed cancers by analyzing individual genetic mutation profiles[3],[4], such diagnostic method takes up considerable amount of time to obtain accurate results. As conventional diagnostic methods involve complicated procedures, simple DNA nanostructures have been introduced to detect cancer biomarkers to facilitate diagnosis.

DNA nanostructures and miRNAs as biomarkers


DNA has emerged as a promising material that allows researchers to construct novel designs as its structure could be predicted easily and accurately.[5] Examples of DNA nanostructures include nano-tweezers to detect norovirus and a DNA ‘Nano-Claw’ to detect membrane markers of cancer cells.[6],[7]

DNA boolean logic gates have been constructed to produce signals in the presence of multiple targets, such as OR-gate and AND-gate DNA tetrahedra that generate fluorescence resonance energy transfer (FRET) signal when multiple inputs hybridize with the probe.[8]

As for the targets to be detected, different micro RNAs (miRNAs) have been identified to be associated with cancers. For example, miR-15b-5p, miR-338-5p, and miR-764 found in plasma are potential biomarkers for detecting hepatocellular carcinoma cancer (HCC), a common type of liver cancer.[9]Therefore, it is promising to use these biomarkers - miRNAs to detect cancers.[10]

Objectives


In vivo synthesis of functional DNA nanostructure


We design a novel DNA nanostructure that detects multiple miRNA targets at the same time, and thus avoiding false positives by promoting discrimination of our detection system. The nanostructure could specify a single base mutation of miRNA while maintaining a relatively low threshold. Our goal is clear - We aim to design a tool which detects a combination of biomarkers and enhance the specificity of detecting particular types of cancer.

In regard to recent in vitro applications of DNA nanostructure, which achieve point-of-care (POC) diagnostics[11], we develop a self-assembled DNA nanostructure that can potentially target miRNAs in vivo. As the content of miRNA targets within the cell is higher than that in the serum, our DNA nanostructure, which is synthesized and assembled in vivo, reduces the need of target amplification. In light of this, our design has an advantage over the existing designs of molecular beacon, which are attached to fluorophores and quenchers[12], and may not be able to be synthesized in vivo. In addition, without attaching to a fluorophore and a quencher, our DNA nanostructure can be produced at a significantly lower cost.

HKU ProjectDescription Mindmap1.jpg


Current progress


Our design is a 3-dimensional structure that can be self-assembled from oligonucleotides. Our aim is to construct a nanostructure that is able to detect multiple miRNA biomarkers such that our design can reach a higher accuracy for diagnosis. For the selection of biomarkers, we are looking for a combination of miRNAs that are specific to a certain type of disease including cancers.

At current stage, we are testing different designs in vitro to see if they can produce desired signals. After proving our designs can work in vitro, we will attempt to test them in vivo. Finally, we will try to design a mechanism such that E. coli can synthesize these oligonucleotides required to form the specified nanostructure.

HKU ProjectDescription Mindmap2.jpg


Signifcances


A leap forward - in vivo synthesis of 3D functional DNA nanostructures


In the past decade, functional DNA nanostructures have been used in similar in vitro approaches to detect various cancer biomarkers.[13][14]It is noted that most of those designs were applied in vitro. Recently, 1D and 2D DNA structures were successfully expressed and assembled in vivo,[15] while several novel 3D DNA structures were synthesized to produce signals in vivo.[16],[17] So given these advancements, our ultimate goal is to allow our functional DNA nanostructure to be synthesized and self-assembled in E. coli, that can function inside the disease cells. This, if successful and with further refinement, could be a great replacement to colour coded surgery in the surgical field.[18]

Last but not least, the cost and quality of production, efficiency and accuracy of our intracellularly-synthesized 3D structure will be compared to current diagnostic methods.

References


  1. ↑ American Cancer Society. (2015). Global Cancer Facts & Figures. Retrieved from http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-044738.pdf
  2. ↑ Public Health England. (2014). National Cancer Intelligence Network Cancer survival in England by stage. Retrieved from http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/survival#ref-3
  3. ↑ Pereira, B., Chin, S., Rueda, O. M., Vollan, H. M., Provenzano, E., Bardwell, H. A., Pugh, M., et al. (2016). The somatic mutation profiles of 2500 primary breast cancers refine their genomic landscapes. Nature Communications
  4. ↑ Pereira, B., Chin, S. F., Rueda, O. M., Vollan, H. K. M., Provenzano, E., Bardwell, H. A., ... & Tsui, D. W. (2016). The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nature communications, 7.
  5. ↑ Chen, Y. J., Groves, B., Muscat, R. A., & Seelig, G. (2015). DNA nanotechnology from the test tube to the cell. Nature nanotechnology, 10(9), 748-760.
  6. ↑ Nakatsuka, K., Shigeto, H., Kuroda, A., & Funabashi, H. (2015). A split G-quadruplex-based DNA nano-tweezers structure as a signal-transducing molecule for the homogeneous detection of specific nucleic acids. Biosensors and Bioelectronics, 74, 222-226.
  7. ↑ You, M., Peng, L., Shao, N., Zhang, L., Qiu, L., Cui, C., & Tan, W. (2014). DNA “nano-claw”: logic-based autonomous cancer targeting and therapy. Journal of the American Chemical Society, 136(4), 1256-1259.
  8. ↑ Pei, H., Liang, L., Yao, G., Li, J., Huang, Q., & Fan, C. (2012). Reconfigurable Three‐Dimensional DNA Nanostructures for the Construction of Intracellular Logic Sensors. Angewandte Chemie, 124(36), 9154-9158.
  9. ↑ Chen, Y., Chen, J., Liu, Y., Li, S., & Huang, P. (2015). Plasma miR-15b-5p, miR-338-5p, and miR-764 as Biomarkers for Hepatocellular Carcinoma. Medical science monitor: international medical journal of experimental and clinical research, 21, 1864.
  10. ↑ Montani, F., & Bianchi, F. (2016). Circulating Cancer Biomarkers: The Macro-revolution of the Micro-RNA. EBioMedicine, 5, 4-6.
  11. ↑ Hartman, Mark R., et al.(2013) . "Point-of-care nucleic acid detection using nanotechnology." Nanoscale 5.21 (2013): 10141-10154.
  12. ↑ TSOURKAS, Andrew, et al. (2003). Hybridization kinetics and thermodynamics of molecular beacons. Nucleic acids research, 2003, 31.4: 1319-1330.
  13. ↑ Miao, P., Wang, B., Chen, X., Li, X., & Tang, Y. (2015). Tetrahedral DNA nanostructure-based microRNA biosensor coupled with catalytic recycling of the analyte. ACS applied materials & interfaces, 7(11), 6238-6243.
  14. ↑ Li W. et. al. (2015). Highly selective and sensitive detection of miRNA based on toehold-mediated strand displacement reaction and DNA tetrahedron substrate. Biosensors and Bioelectronics. 71, 401-406.
  15. ↑ Elbaz, J., Yin, P., & Voigt, C. A. (2016). Genetic encoding of DNA nanostructures and their self-assembly in living bacteria. Nature communications, 7.
  16. ↑ Kim K. et. al. (2013). Drug delivery by self-assembled DNA tetrahedron for overcoming drug resistance in breast cancer cells. Chem. Commun. 49, 2010-2012.
  17. ↑ Kim K. et. al. (2013). Sentinel lymph node imaging by a fluorescently labeled DNA tetrahedron. Biomaterials. 34, 5226-5235.
  18. ↑ Nguyen, Q. T., & Tsien, R. Y. (2013). Fluorescence-guided surgery with live molecular navigation [mdash] a new cutting edge. Nature reviews cancer, 13(9), 653-662.