김대식 교수
Dae-Sik Kim
성균관대학교 의학과 · 생화학·유전·분자생물학
연구실 소개
김대식 교수의 연구실은 유전자 편집 기술의 정밀성과 안정성을 높이기 위한 신뢰도 높은 오프타겟 분석 기법을 개발하고 있으며, 특히 Digenome-seq를 비롯한 in vitro 유전자 편집 특이성 평가 시스템을 핵심으로 연구를 진행하고 있습니다. CRISPR-Cas9 및 프라임 에이저와 같은 정밀 유전자 편집 도구의 오프타겟 활성과 크로마틴 환경이 미치는 영향을 체계적으로 분석함으로써, 향후 치료적 응용에 필수적인 안전성 확보를 목표로 하고 있습니다. 또한, 유전자 편집 도구의 기초 메커니즘과 세포 내 환경 요인 간의 상호작용에 대한 통합적 이해를 추구하고 있습니다.
연구 현황
연구 성과 추이
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
주요 논문
15We present multiplex Digenome-seq to profile genome-wide specificities of up to 11 CRISPR-Cas9 nucleases simultaneously, saving time and reducing cost. Cell-free human genomic DNA was digested using multiple sgRNAs combined with the Cas9 protein and then subjected to whole-genome sequencing. In vitro cleavage patterns, characteristic of on- and off-target sites, were computationally identified across the genome using a new DNA cleavage scoring system. We found that many false-positive, bulge-typ
Programmable nucleases and deaminases, which include zinc-finger nucleases, transcription activator-like effector nucleases, CRISPR RNA-guided nucleases, and RNA-guided base editors, are now widely employed for the targeted modification of genomes in cells and organisms. These gene-editing tools hold tremendous promise for therapeutic applications. Importantly, these nucleases and deaminases may display off-target activity through the recognition of near-cognate DNA sequences to their target sit
Prime editors (PEs) enable targeted precise editing, including the generation of substitutions, insertions and deletions, in eukaryotic genomes. However, their genome-wide specificity has not been explored. Here, we developed Nickase-based Digenome-seq (nDigenome-seq), an in vitro assay that uses whole-genome sequencing to identify single-strand breaks induced by CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) nickase. We used nDigenome-seq t
To investigate whether and how CRISPR-Cas9 on-target and off-target activities are affected by chromatin in eukaryotic cells, we first identified a series of identical endogenous DNA sequences present in both open and closed chromatin regions and then measured mutation frequencies at these sites in human cells using Cas9 complexed with matched or mismatched sgRNAs. Unlike matched sgRNAs, mismatched sgRNAs were highly sensitive to chromatin states, suggesting that off-target but not on-target DNA
Advanced glycation end products (AGEs) have long been considered as potent molecules promoting neuronal cell death and contributing to neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we demonstrate that AGE-albumin, the most abundant AGE product in human AD brains, is synthesized in activated microglial cells and secreted into the extracellular space. The rate of AGE-albumin synthesis in human microglial cells is markedly increased by amyloid-β exposure and oxidative
Electronic skin (E-skin) based on tactile sensors has great significance in next-generation electronics such as biomedical application and artificial intelligence that requires interaction with humans. To mimic the properties of human skin, high flexibility, excellent sensing capability, and sufficient spatial resolution through high-level sensor integration are required. Here, we report a highly sensitive pressure sensor matrix based on a piezoresistive cellulose/single-walled carbon nanotube-e
In this work, we introduce a novel algorithm for solving the textbook question answering (TQA) task which describes more realistic QA problems compared to other recent tasks. We mainly focus on two related issues with analysis of the TQA dataset. First, solving the TQA problems requires to comprehend multimodal contexts in complicated input data. To tackle this issue of extracting knowledge features from long text lessons and merging them with visual features, we establish a context graph from t
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