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Biomedical subjects

Seung Hwan Lee

Publications and source records attributed to Seung Hwan Lee.

4 recordsLinked to original sources

Advances in large-scale DNA engineering with the CRISPR system.

In recent years, DNA engineering technology has undergone significant advancements, with clustered regularly interspaced short palindromic repeats (CRISPR)-based target-specific DNA insertion emerging as one of the most rapidly expanding and widely studied approaches. Traditional DNA insertion technologies employing recombinases typically involve introducing foreign DNA into genes in vivo by either pre-engineering recognition sequences specific to the recombinase or through genetic crossing to incorporate the requisite recognition sequence into the target gene. However, CRISPR-based gene insertion technologies have advanced to streamline this engineering process by combining the CRISPR-Cas module with recombinase enzymes. This process enables accurate and efficient one-step insertion of foreign DNA into the target gene in vivo. Here we provide an overview of the latest developments in CRISPR-based gene insertion technologies and discusses their potential future applications.

CRISPR-Cas Systems↗

Precise progerin targeting using RfxCas13d: A therapeutic avenue for Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS), an extremely rare progressive genetic disorder, is caused by a point mutation in LMNA that induces progerin production, which disrupts cellular function and triggers premature aging and mortality. Despite extensive efforts, HPGS remains incurable. We successfully implemented a strategy using RfxCas13d to selectively target progerin mRNA at specific junction regions, without unintended cleavage and reduce its expression. This technique discriminated between normal lamin A and progerin, thus providing a safe and targeted therapeutic avenue to treat HGPS. Our approach effectively restored aberrant gene expression and progerin-induced cellular phenotypes, including senescence, mitochondrial dysfunction, and DNA damage in cells with HGPS and LMNAG608G/G608G mice. Notably, LMNAG608G/G608G mice exhibited improved progeroid phenotypes, suggesting a potential therapeutic application of this approach for other diseases resulting from abnormal RNA splicing.

Progeria↗

Innate immunity to cytomegalovirus: the Cmv1 locus and its role in natural killer cell function.

The identification and characterization of genetic loci that contribute to patterns of susceptibility/resistance to infection provide important insights into the mechanisms of innate and adaptive immunity. Genetic heterogeneity across the population makes the characterization of such traits in humans technically difficult; however, inbred animal models represent an ideal tool for such analyses. This review illustrates the power of mouse genetics as utilized for the identification and characterization of the locus conferring early resistance to murine cytomegalovirus infection, Cmv1. This locus encodes an activating C-type lectin receptor of the Ly49 family that promotes natural killer (NK) cell cytolysis of infected cells. Although NK cells are usually able to detect and destroy virally infected cells via recognition of the downregulation of MHC class I molecules, the Cmv1 locus provides the first example of an NK receptor that is able to mediate clearance of viral infection via direct recognition of a virally encoded protein.

Animals↗