San Hae Im

220, E6-6, KAIST

291, Daehak-ro

Yuseong-gu, Daejeon

I completed my Ph.D. degree in the Department of Biological Sciences at Korea Advanced Institute of Science and Technology (KAIST) under my advisor, Prof. Hyun jung Chung.

My research focused on the topic of “Engineered nanoparticle systems for gene therapeutic and diagnostics.” More specifically, I studied advanced nanoparticle systems for CRISPR/Cas9 cancer therapy, mRNA vaccination, and antibiotic-resistant bacteria detection.

Currently, I am working on the development of an effective CRISPR/Cas9 mRNA delivery system via lipid nanoparticles for cancer therapy.

selected publications

2024

A Wireless, CRISPR-Polymer Dot Electrochemical Sensor for the Diagnosis of Bacterial Pneumonia and Multi-Drug Resistance

San Hae Im†, Akhmad Irhas Robby†, Heewon Choi, and 4 more authors

ACS Applied Materials & Interfaces, 2024

PMID: 38278531

Abs

Rapid and accurate diagnosis is crucial for managing the global health threat posed by multidrug-resistant bacterial infections, however, current methods have limitations in either being time-consuming, labor-intensive, or requiring instruments with high costs. Addressing these challenges, we introduce a wireless electrochemical sensor integrating the CRISPR/Cas system with electroconductive polymer dot (PD) nanoparticles to rapidly detect bacterial pathogens from human sputum. To enhance the electroconductive properties, we synthesized copper-ion immobilized PD (PD-Cu), followed by conjugation of the deactivated Cas9 protein (dCas9) onto PD-Cu-coated Si electrodes to generate the dCas9-PD-Cu sensor. The dCas9-PD-Cu sensor integrated with isothermal amplification can specifically detect target nucleic acids of multidrug-resistant bacteria, such as the antibiotic resistance genes kpc-2 and mecA. The dCas9-PD-Cu sensor exhibits high sensitivity, allowing for the detection of 54 femtograms of target nucleic acids, based on measuring the changes in resistivity of the Si electrodes through target capture by dCas9. Furthermore, a wireless sensing platform of the dCas9-PD-Cu sensor was established using a Bluetooth module and microcontroller unit for detection using a smartphone. We demonstrate the feasibility of the platform in diagnosing multidrug-resistant bacterial pneumonia in patients’ sputum samples, achieving 92% accuracy. The current study presents a versatile biosensor platform that can overcome the limitations of conventional diagnostics in the clinic.
Finely Tuned Ionizable Lipid Nanoparticles for CRISPR/Cas9 Ribonucleoprotein Delivery and Gene Editing

San Hae Im†, Mincheol Jang†, Ji-Ho Park*, and 1 more author

Journal of Nanobiotechnology, 2024

Abs

Nonviral delivery of the CRISPR/Cas9 system provides great benefits for in vivo gene therapy due to the low risk of side effects. However, in vivo gene editing by delivering the Cas9 ribonucleoprotein (RNP) is challenging due to the poor delivery into target tissues and cells. Here, we introduce an effective delivery method for the CRISPR/Cas9 RNPs by finely tuning the formulation of ionizable lipid nanoparticles. The LNPs delivering CRISPR/Cas9 RNPs (CrLNPs) are demonstrated to induce gene editing with high efficiencies in various cancer cell lines in vitro. Furthermore, we show that CrLNPs can be delivered into tumor tissues with high efficiency, as well as induce significant gene editing in vivo. The current study presents an effective platform for nonviral delivery of the CRISPR/Cas9 system that can be applied as an in vivo gene editing therapeutic for treating various diseases such as cancer and genetic disorders.

2023

Bioorthogonal CRISPR/Cas9-Drug Conjugate: A Combinatorial Nanomedicine Platform

Marcel Janis Beha†, Joo-Chan Kim†, San Hae Im†, and 7 more authors

Advanced Science, 2023

Abs

Bioconjugation of proteins can substantially expand the opportunities in biopharmaceutical development, however, applications are limited for the gene editing machinery despite its tremendous therapeutic potential. Here, a self-delivered nanomedicine platform based on bioorthogonal CRISPR/Cas9 conjugates, which can be armed with a chemotherapeutic drug for combinatorial therapy is introduced. It is demonstrated that multi-functionalized Cas9 with a drug and polymer can form self-condensed nanocomplexes, and induce significant gene editing upon delivery while avoiding the use of a conventional carrier formulation. It is shown that the nanomedicine platform can be applied for combinatorial therapy by incorporating the anti-cancer drug olaparib and targeting the RAD52 gene, leading to significant anti-tumor effects in BRCA-mutant cancer. The current development provides a versatile nanomedicine platform for combination treatment of human diseases such as cancer.
Fabrication of Scratched Nanogrooves for Highly Oriented Cell Alignment and Application as a Wound Healing Dressing

Min Jeong Shin†, San Hae Im†, Baekman Kim†, and 7 more authors

ACS Applied Materials & Interfaces, 2023

PMID: 37014981

Abs

Using improper wound care materials may cause impaired wound healing, which can involve scar formation and infection. Herein, we propose a facile method to fabricate a cell-alignment scaffold, which can effectively enhance cell growth and migration, leading to the reproduction of cellular arrangements and restoration of tissues. The principle is scratching a diamond lapping film that gives uniaxial nanotopography on substrates. Cells are seeded to follow the geometric cue via contact guidance, resulting in highly oriented cell alignment. Remarkable biocompatibility is also demonstrated by the high cell viability on various substrates. In vivo studies in a wound healing model in mice show that the scratched film supports directed cell guidance on the nanostructure, with significantly reduced wound areas and inhibition of excessive collagen deposition. Rapid recovery of the epidermis and dermis is also shown by histological analyses, suggesting the potential application of the scratching technique as an advanced wound dressing material for effective tissue regeneration.

2022

Recyclable Periodic Nanostructure Formed by Sublimable Liquid Crystals for Robust Cell Alignment

Min Jeong Shin†, San Hae Im†, Wantae Kim, and 4 more authors

Langmuir, 2022

PMID: 35302783

Abs

We demonstrate a facile method to fabricate a recyclable cell-alignment scaffold using nanogrooves based on sublimable liquid crystal (LC) material. Randomly and uniaxially arranged smectic LC structures are obtained, followed by sublimation and recondensation processes, which directly produce periodic nanogrooves with dimensions of a couple of hundreds of nanometers. After treatment with osmium tetroxide (OsO4), the nanogroove can serve as a scaffold to efficiently induce directed cell growth without causing cytotoxicity, and it can be used repeatedly. Together, various cell types are applied to the nanogroove, proving the scaffold’s broad applicability. Depending on the nanotopography of the LC structures, cells exhibit different morphologies and gene expression patterns, compared to cells on standard glass substrates, according to microscopic observation and qPCR. Furthermore, cell sheets can be formed, which consist of oriented cells that can be repeatedly formed and transferred to other substrates, while maintaining its organization. We believe that our cell-aligning scaffold may pave the way for the soft material field to bioengineering, which can involve fundamentals in cell behavior and function, as well as applications for regenerative medicine.