The result of China's Third National Death Survey Report showed that cancer was the second cause of death in the country ( the mortality rate was 1.3588 / 1000 ), while it was the first one in the city ( the mortality rate was 1.5018/1000 ), which was much higher than the cerebrovascular disease. At the end of cancer, cancerous cells spread rapidly and are difficult to be completely eradiated, as a result, many researchers have been focusing on the early detection and treatment of cancer. There are some methods of early detection of cancer such as using urine autofluorescence spectroscopy[1] and Quantum dots, a kind of molecular image probe[2]. However, there are large limitations on their specificity and operability, etc. So it is necessary to find an early and effective method for detecting cancer with high efficiency and operability.
②It is known that in cancerous cells, a change in the rate of oxidative stress, lipid peroxidation, and gene sequences leads to abnormalities in the biochemical pathways of these cells and thus to the production of specific volatile organic compounds ( VOCs )[3]. Besides, the deteriorated food and the contaminated water will also have specific VOCs.
③The specific olfactory receptors can be combined with specific VOCs to initiate the cAMP pathway ( Fig.1 ).
Fig.1. Pathway of signal transduction in olfactory sensory neurons. The odorant receptor defines odorant responsiveness. It involves G protein receptors, adenylyl cyclase, Na/Ca channels and Cl channels in order to produce an electric potential in the olfactory neurons.
④The traits of the CRISPR/Cas9 system is similar to those of the restriction endonucleases, its specific cleavage of the sequence mainly relies on the binding of the nucleus complexes formed by the crRNA and Cas9 proteins to identify the PAM and the protospacer on the target sequence. Scientists have employed this targeted CRISPR/Cas9 system to modulate gene expression by concatenating the cutting-deficient Cas9 with gene regulatory domains.
Taken together, the project aims to engineer an artificial olfactory receptor activation system in the cultured mammalian cells with CRISPR-based gene activation system in order to achieve greater sensitivity to the trace amount of VOCs than previous approaches. This intensified smeller (iSmeller) holds great potential to be developed as novel accurate and convenient biological sensor in the early detection of cancer as well as food quality control and environmental pollution evaluation.
References
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Wang HN, Meng XX, Zhou KD, Ren QS, Sun HF, Application of Molecular Imaging Probes - Quantum Dots in Cancer Imaging and Early Detection [J]. China Medical Devices, 2015, 04.
A Pomerantz, R Blachman-Braun, JA Galnares-Olalde, R Berebichez-Fridman, M Capurso-García, The possibility of inventing new technologies in the detection of cancer by applying elements of the canine olfactory apparatus [J]. Medical Hypotheses 85 (2015) 160–172.
Fang R, Chang F, Sun ZL, Li N, Meng QY, New Method of Genome Editing Derived From CRISPR/Cas9 [J]. Progress in Biochemistry and Biophysics, 2013, 40(8): 691-702.
