Biomedical subjects

Kyung Hyun Lee

Publications and source records attributed to Kyung Hyun Lee.

5 recordsLinked to original sources

PubMed2026

Target site selection and P1 engineering enable highly efficient circular RNA production via end-to-end self-targeting and splicing.

Circular RNAs (circRNAs) are more stable than linear RNAs, enabling expanding applications in RNA vaccines and therapeutics. We previously developed an in vitro circRNA preparation method based on end-to-end self-targeting and splicing (STS) using the Tetrahymena group I intron, which generates circRNAs without extraneous sequences. However, self-circularization efficiency declines as gene of interest (GOI) length increases, limiting its application to longer GOIs. Here, we systematically optimized key determinants of STS efficiency, including target site selection and P1 construct engineering. Target site screening revealed that selection of optimal target sites within each GOI markedly improved self-circularization efficiency. Moreover, engineering of the P1 construct, including incorporation of a polyA10 sequence upstream of the internal guide sequence of the intron and an antisense sequence complementary to the target site and its upstream region at the 5' side of polyA10, further enhanced efficiency. Notably, the optimized STS strategy achieved up to two-fold higher self-circularization efficiency than the conventional permuted intron-exon (PIE) method for long GOIs (∼8 K-nt). Collectively, these results establish an improved STS workflow for efficient circRNA production without extraneous sequences across a wide range of GOI lengths, outperforming the PIE method for long GOIs, and broadening biomedical applications.

RNA, Circular↗

PubMed2006

A strategy for the design of selective RNA binding agents. Preparation and RRE RNA binding affinities of a neomycin-peptide nucleic acid heteroconjugate library.

We have successfully developed a new strategy for RNA ligand design, which applies the antisense concept to enhance and make more specific loop region interactions while at the same time preserving stem region anchoring. The heteroconjugates, prepared in this effort, have proven to be the most specific small molecule ligands against RRE RNA that have been uncovered to date.

Drug Design↗

PubMed2005

A hybrid molecule that prohibits amyloid fibrils and alleviates neuronal toxicity induced by beta-amyloid (1-42).

Inhibition of oligomeric amyloid beta (Abeta) peptide or fibril formation has emerged as a major therapeutic target for developing new drugs for Alzheimer's disease. We focused on developing inhibitors by synthesizing hybrid molecules of ferulic acid and styryl benzene, which has been known as a fibril binder. Initially, cell-based assay was carried out to evaluate the effective compound. A selected effector, 1, alleviated the Abeta-induced neuronal toxicity in differentiated SH-SY5Y human neuroblastoma cells. The effector could also inhibit Abeta fibril formation, monitored by thioflavin T fluorescence intensity assay and transmitted electron microscopic images. A strong binding affinity of 1 to non-fibrous monomer-like Abeta, which was immobilized to a surface chip, was measured using a surface plasmon resonance technique. The data suggest that the effector shifts the equilibrium of multimeric Abeta, inhibiting the pathogenic oligomer or fibril formation.

Amyloid beta-Peptides↗

PubMed2004

An approach to enhance specificity against RNA targets using heteroconjugates of aminoglycosides and chloramphenicol (or linezolid).

We describe the design and synthesis of new heterodimeric conjugates, which are comprised of a neomycin B (Neo) stem-binding component and a chloramphenicol (Cam) or linezolid (Lnz) loop-binding component. Some of the heterodimeric conjugates display enhanced affinities to RNA targets and that binding occurs in both stem and loop regions of the RNA. In addition, the results of foot-printing and mutation studies suggest that the enhanced binding affinity of the conjugates is RNA sequence-specific.

Acetamides↗

PubMed2002

Mimicry of tandem repeat peptides against cell surface carbohydrates.

Our approach to multivalent peptide construction relies on tentacle peptides, also known as a multiple antigenic peptides, which contain two and four repeats of a selected peptide. In this communication, we report the results of preliminary studies aimed at (1) the selection of short peptides against the carbohydrate, sLeX, (2) the synthesis of tentacle dimers and tetramers of the selected peptides, and (3) the determination of affinities and specificities of the peptides to several related carbohydrates by using the surface plasmon resonance (SPR) and the equilibrium dialysis techniques. Binding affinity studies, as well as assays of in vitro binding of the peptides to a sLeX-specific cell line, have shown that the tetrameric peptides bind to the cell surface sugars.

Amino Acid Sequence↗