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Biomolecular Engineering / Chemical Biology / Nanotherapeutics

Protein Design and Engineering (단백질 공학 및 분자 진화)

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

Taking the advantage of proteins as a magic bullet, we are developing a human-originated scaffold protein as an artificial antibody for targeted therapy. To do this, we are exploiting a high-throughput screening system (Phage display) and a computational design (AI-based structure prediction) to confer a protein binder with high specificity and affinity towards a disease-related antigen (iScience 2021). In addition, based on crystal structure, we are rationally modifying and optimizing biochemical properties as well as the function of proteins (Mol Ther 2014, ChemBioChem 2023).

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

Rational Design of Therapeutic Bioassemblies (생체분자 기반 치료용 나노입자 개발)

Nanostructured materials have been increasingly developed for a wide range of biomedical applications including bioimaging and theragnosis, due to their multifunctionality and designability. Especially, various nanoparticulate systems have been exploited in fabricating nanoscale drug formulations and have successfully shown a great potential for the effective delivery of anticancer drugs with prolonged circulation time and enhanced tumor accumulation. Although the distinctive properties make them a promising drug delivery vehicle for cancer therapy, most conventional systems are chemically synthesized and polymerized under harsh conditions such as in organic solvents with complex and multiple reaction steps. Thus, the synthetic nanoparticles have intrinsic limitations related to productivity, homogeneity, and biosafety.

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

Artificial Antibody Engineering (인공항체 기반 바이오 혁신신약 개발)

We have already developed a non-antibody scaffold protein using a repeat protein consisting of leucine-rich repeat (LRR) modules (PNAS 2012). The scaffold protein, termed 'Repebody', exhibited considerable biophysical stability and a high bacterial expression level, leading to the successful development of various molecular binders for IL-6 and EGFR (Mol Ther 2014, Angew Chem 2015). Notably, the resulting repebodies showed strong anti-cancer activity in vivo comparable to conventional monoclonal antibodies. Through the platform scaffold, we are actively developing a novel protein therapeutic using a modular evolution method for the treatment of various types of diseases including cancers and autoimmune diseases.

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 responding to numerous cellular signals. Even though the DNA topological changes are one of the most complex and dynamic biological processes, they are spatially and temporally well controlled with a significantly lower number of errors. It is believed that this remarkable feature of DNA results from canonical Watson-Crick base pairing and an infinite number of combinations of nucleotide sequences.

Interestingly, single-stranded DNAs (ssDNAs) are precisely associated with a form of crosslinked dsDNAs in a sequence-guided manner by dictating hydrogen bonds and the shape complementary between bases of each other. Due to the ease of sequence-based design of DNA in a rational manner, DNAs have been considered one of the most promising building blocks in the field of nanotechnology and nanomaterials for developing highly organized and self-assembling nanoarchitectures that are precisely designed at the near-atomic level. Thus, structural DNA nanotechnology has emerged and offered an unprecedented way of enabling the effective construction of precisely controlled nanoassemblies with a well-defined shape and size. Based on the 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)

모두가 비슷한 생각을 한다는 것은, 아무도 생각하고 있지 않다는 말이다 - 아인슈타인

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