Development of an ultrafast cancer cell gene diagnostic technology 

using bio-fused gold nano-particles

The research team of Professor Sang Jun Sim was successful in developing a biosensor that can accurately and quickly detect gene mutations.

The results were published in the international journal, Nature Communications.

▲ Professor Sang Jun Sim (corresponding author, left), Dr. Xingyi Ma(primary author, right)

The research team of Professor Sang Jun Sim (Department of Chemical & Biological Engineering, College of Engineering) has developed a biosensor based on bio-fused gold nanoparticles that can detect mutations in cancer cell genes quickly and accurately

The research was conducted with support from the Ministry of Science and ICT, the Basic Research Project (Mid-career Program) and Technology Development Program to Solve Climate Changes (Korea CCS 2020) of the National Research Foundation of Korea, and CODI-M Co., Ltd. and the results were published in the international journal, Nature Communications, on February 19.

- Title: Single gold-bridged nanoprobes for identification of single point DNA mutations

- Authors: Dr. Xingyi Ma (Primary author. Korea University), Sojin Song (Korea University), Soohyun Kim (Korea University), Dr. Mi-sun Kwon (Seoul National University), Professor Hyunsook Lee (Seoul National University), Professor Wounjhang Park (University of Colorado), Professor Sang Jun Sim (Corresponding author, Korea University)

Interest in genetic testing for the early diagnosis and prevention of breast cancer is high. It began to attract more interest in 2013 when American actress, Angelina Jolie discovered a mutation in her BRCA1 gene and received a preventative mastectomy. The BRCA1 gene plays a role in restoring damaged intracellular DNA and inhibiting tumors, and when mutation occurs, the incidence of breast cancer reaches 80%. Although many techniques have been developed for precise gene mutation detection, there are still limitations in terms of detection time and sensitivity

Using the gold nanoparticle’s sensitivity to light, the team developed a biosensor that detects point mutations in genes. In just 2 minutes, the mutation can be precisely detected at the molecular level

* Point Mutation: Mutation that occurs when one of the bases constituting DNA is transformed

To restore the gene, MutS protein binds to the point mutation, which is detected by the scattered light changes of the gold nanoparticles. In order to significantly improve the sensitivity of gold nanoparticles, the sensor was designed in the form of a 'nanobridge'(rather than a regular ball or rod shape) in which two particles are connected. By applying the developed gold nanoparticle biosensor, the team succeeded in diagnosing not only the presence of point mutation in the cancer cell line but also the type of mutation. The team used the principle that the different types of point mutations are affected by the binding rate of MutS protein.

Professor Sim commented on the background and the significance of the research in stating that, "This research is an optical platform technology that greatly improves the sensitivity to light through the unique form of single nanoparticles. Because it is easy and fast to diagnose various genetic diseases in real time with only a very small sample, it will be widely used in the medical field for patient-tailored treatment."

(Figure 1) Comparison of sensitivities of particles by type and construction of 'nanobridge' structure

By analyzing the peak shift of the scattered light versus the refractive index of the surrounding medium of gold nanoparticles of four different shapes, it was confirmed that the nanobridge structure has the highest sensitivity to light and the particles of the relevant structure are fabricated.

(Figure 2) Kinetic analysis of 8 BRCA1 gene point mutations

Kinetic analysis of the interaction with the MutS protein according to the types of point mutations occurring on the BRCA1 gene showed the speed constant in the order of GT> GG> + C> AA> TC> -C> AC>GA.

(Figure 3) Point mutation analysis of the BRCA1 gene in 2 cancer cell lines

Analysis of the point mutation type of BRCA1 gene present in a cancer cell line (left: breast cancer, right: ovarian cancer). An insertion mutation(+C) was detected in the breast cancer cell line (HCC1937) and a substitution mutation(G>A) was detected in the ovarian cancer cell line (SNU-251).