OUR APPROACH

Advancing Innovative Science and Technology

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ߊ Design Protein De Novo from Nature 

We are now entering an era of rational protein design for therapeutic purpose by integrating knowledges across bioinformatics, structural biology, and de novo design. Designing a protein with predetermined structure and function once viewed formidable has now become possible and increasingly used in modern drug design. At IMNEWRUN, we design proteins de novo sampled from nature’s backbone fragments via computational approach. This enables us rationally designed experimental library such as yeast display in a most efficient way to evaluate proteins with the desired function.

 

The TRANSMAB® technology is proprietary and novel approach for delivering a therapeutic antibody selectively to brain by genetically incorporating peptide selected from the TRANSPEP® library. The library has been constructed based on our inspection of the cryo-electron microscopic (cryo-EM) structure of human transferrin receptor and use our acumen to design peptides de novo.

All atom imposition with electron density by 2.7Å (590k single particle analysis).

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Scheme of Peptide Design for Receptor Binding

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Internal Cryo-EM Data of Human Transferrin Receptor

William DeGrado is a Professor of Department of Pharmaceutical Chemistry at the University of California, San Francisco (UCSF) and a member of the National Academy Sciences. He was the first to successfully design and construct a protein “from scratch” and pioneered the design of peptides that not only fold into protein-like structures but also incorporate desired functionalities. Prof. DeGrado has been our scientific advisor for various technology platforms being developed by IMNEWRUN.

Yong Ho Kim is an Associate Professor of SKKU Advanced Institute of Nanotechnology (SAINT) & Department of Nano Engineering at the Sungkyunkwan University (SKKU). He is also a co-founder and Vice President leading the Protein Design team at IMNEWRUN. Under his leadership and in close academic collaboration with his laboratory, IMNEWRUN creates advanced technology platforms and treatment modalities to address challenging medical unmet needs.

ߊ Discover Biology from Patient’s Cell 

Induced pluripotent stem cell (iPSC) technology has been a paradigm shift in disease modeling, drug development and precision medicine. Recent advances include reprogramming a patient’s somatic cells into iPSC and differentiate these cells into disease-relevant cell types for in vitro screening platform for drug evaluation.

 

At IMNEWRUN, we are exploring molecular mechanism of various disease using iPSC and genome editing techniques through close academic collaboration with Jaecheol Lee, Assistant Professor of the School of Pharmacy, SKKU and his laboratory. Prof. Lee is also Vice President leading the Discovery Biology team at IMNEWRUN. Under his leadership, we explore the fundamental science and mechanism of action for various technology platforms and treatment modalities being developed at IMNEWRUN.

iPSC-derived motor neuron, brain, and heart organoids

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Source: J-Lab with courtesy of Prof. JC Lee

(A) Representative confocal images of iPSC derived motor neuron (MN). iPSC-MN were stained with specific antibodies against ISL1(red) and SMI32(green). Blue represented HOECHST staining. (B) Representative bright-field image of iPSC derived brain organoid (cerebral organoid) (left). Representative confocal images of iPSC-brain organoid (right). iPSC-brain organoid were stained with specific antibodies against SOX2(red) and TUJ1(white). Blue represented HOECHST staining. (C) Representative confocal images of iPSC derived heart organoid (HO) (left and middle). iPSC-HO were stained with specific antibodies against TNNT2(red), GOL1A1(green) and NFATC1(green). Blue represented HOECHST staining. Representative bright-field movie of iPSC-HO (right).

ߊ Real-Time Imaging through Brain Window

While the TRANSMAB® technology provides a turn-key solution for delivering a therapeutic antibody selectively to brain, evaluation of blood-brain-barrier (BBB) penetration of the therapeutic antibody to brain poses another significant challenge.

We have delicate and sophisticated in-house knowhow for the evaluation of brain penetration of a large molecule. We developed longitudinal live imaging and qualification method through in vivo cranial window system. This provides bona fide real-time data on BBB penetration.

In vivo Longitudinal BBB Penetration of TRANSMAB®

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Real-Time BBB Transcytosis

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Left. Intravascular (upper panel) and extravascular (lower panel) intensities from the in vivo longitudinal two-photon microscopic images of BBB transcytosis of TRANSMAB® conjugated with Alexa-568 at various time points of 1, 4, 7 and 10 days in Tie2-GFP Tg mouse with a glass-cranial window implantation. Longitudinal images were taken from the cortical layer II/III of Tg mouse. Color bar indicate TRANSMAB® concentration. Right. Real-time imaging of BBB transcytosis was taken for 20 min at 2 min interval on the 4 days after administration. Red color indicate TRANSMAB® and Green color indicate Tie2+ endothelial cell. The white dotted boundary indicates the vessel wall, and the Intra/Extravascular area are separated by the boundary.

Minah Suh is a Professor of Department of Biomedical Engineering, SKKU. She is also a co-founder and Vice President leading the In Vivo Pharmacology team at IMNEWRUN. Under her leadership and in close academic collaboration with the her laboratory, we explore the underlying mechanism and its proof-of-concept for evaluation of various technology platforms and treatment modalities being developed by IMNEWRUN.