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Biomolecular Engineering / Chemical Biology / Nanobiotechnology

Protein Engineering and Design (단백질 공학 및 설계)

Recently, protein therapeutics have been considered an emerging star in targeted cancer therapy due to their high potency and low toxicity. The remarkable efficacy is closely linked to the intrinsic property of proteins, which can specifically bind to an antigen without cross-reactivity or non-specific binding.

Taking advantage of proteins as a magic bullet, we are developing a human-originated scaffold protein as an artificial antibody for targeted therapy. To achieve this, we are utilizing a high-throughput screening system (Phage display) and AI-based biomolecular design tools (AlphaFold3, RFdiffusion, ProteinMPNN) to engineer a protein binder with high specificity and affinity toward a disease-related antigen (iScience 2021). In addition, based on crystal structures, we are rationally modifying and optimizing the biochemical properties and functions of the proteins (Mol Ther 2014, ChemBioChem 2023).

관련보도자료: 우리 기술로 단백질 신약 개발한다! (YTN 2012)

Advanced Theragnostic Systems (생체분자 기반 동반진단용 나노시스템 개발)

Nanostructured materials have been increasingly developed for a wide range of biomedical applications, including bioimaging and theragnosis, due to their multifunctionality and designability. In particular, various nanoparticulate systems have been exploited to fabricate nanoscale drug formulations and have demonstrated significant potential for the effective delivery of anticancer drugs, offering prolonged circulation time and enhanced tumor accumulation. Although these distinctive properties make them promising drug delivery vehicles for cancer therapy, most conventional systems are chemically synthesized and polymerized under harsh conditions, such as in organic solvents, involving complex and multiple reaction steps. Consequently, synthetic nanoparticles have intrinsic limitations regarding productivity, homogeneity, and biosafety.

To overcome these obstacles, nanoparticles based on naturally occurring molecules (e.g., DNA, peptide, and protein) have recently emerged as an attractive alternative to synthetic materials. Among them, proteins are biofunctional molecules with well-defined molecular sizes at the nanometer scale. They possess the ability to precisely recognize specific target molecules and spontaneously assemble into well-ordered and stable supramolecular structures, thereby facilitating the scalable production of nanoscale particles with homogeneous size distribution. In addition, because all proteins consist of unique amino acid sequences, protein-based particles can be easily modified and optimized through simple genetic engineering, enabling site-specific functionalization with targeting moieties and active protein cargos. Based on these advantages, we are designing and engineering protein nanoassemblies as smart biomaterials for cancer diagnosis and therapy (Angew Chem 2015, Biomaterials 2017, Biosens Bioelectron 2025).

Artificial Antibody Engineering (인공항체 기반 고효능 바이오 혁신신약 개발)

We have already developed a non-antibody scaffold protein based on a repeat protein consisting of leucine-rich repeat (LRR) modules (PNAS 2012). The scaffold protein, termed 'Repebody', exhibits considerable biophysical stability and a high bacterial expression level, which has enabled the successful development of various molecular binders targeting IL-6 and EGFR (Mol Ther 2014, Angew Chem 2015). Notably, the resulting Repebodies demonstrated strong anticancer activity in vivo, comparable to that of conventional monoclonal antibodies. Using this platform scaffold, we are actively developing novel protein therapeutics through a modular evolution approach for the treatment of various diseases, including cancer and autoimmune disorders.

관련보도자료: 항암제 투과율·암세포사멸능력 높인 항체-약물복합체 개발 (연합뉴스 2015)

Nucleoprotein Nanostructures (다기능성 핵산-단백질 나노구조체 설계)

During transcription and DNA replication, double-stranded DNAs (dsDNAs) are dynamically dissociated and re-assembled in response to numerous cellular signals. Although DNA topological changes represent one of the most complex and dynamic biological processes, they are spatially and temporally well controlled with a remarkably low error rate. It is believed that this remarkable feature of DNA results from canonical Watson-Crick base pairing and the vast number of possible nucleotide sequence combinations.

Interestingly, single-stranded DNAs (ssDNAs) precisely assemble into crosslinked dsDNAs in a sequence-guided manner through hydrogen bonding and shape complementarity between bases. Owing to the ease of rational, sequence-based design of DNA, DNA has been considered one of the most promising building blocks in the field of nanotechnology and nanomaterials for developing highly organized, self-assembling nanoarchitectures that can be precisely designed at the near-atomic level. Thus, structural DNA nanotechnology has emerged, offering an unprecedented means of constructing precisely controlled nanoassemblies with well-defined shapes and sizes. Based on these notable advantages of DNA, we are rationally designing and creating a variety of programmable DNA nanostructures with spatially partitioned functions (Small 2018, Nanoscale 2020) for realizing smart cancer nanotherapy with precision diagnostics.

관련보도자료: DNA 나노구조체로 단백질 치료제 효율 높였다 (YTN 사이언스 2019)

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