Development of End-Spliced Dimeric Nanodiscs for the Improved Virucidal Activity of a Nanoperforator

Hyunseok Oh, Younghun Jung, Seokoh Moon, Jaehyeon Hwang, Choongjin Ban, Jinhyo Chung, Woo Jae Chung, Dae Hyuk Kweon

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Lipid-bilayer nanodiscs (NDs) wrapped in membrane scaffold proteins (MSPs) have primarily been used to study membrane proteins of interest in a physiological environment. Recently, NDs have been employed in broader applications including drug delivery, cancer immunotherapy, bio-imaging, and therapeutic virucides. Here, we developed a method to synthesize a dimeric nanodisc, whose MSPs are circularly end-spliced, with long-term thermal stability and resistance to aggregation. The end-spliced nanodiscs (esNDs) were assembled using MSPs that were self-circularized inside the cytoplasm ofEscherichia colivia highly efficient protein trans-splicing. The esNDs demonstrated a consistent size and 4-5-fold higher stability against heat and aggregation than conventional NDs. Moreover, cysteine residues on trans-spliced circularized MSPs allowed us to modulate the formation of either monomeric nanodiscs (essNDs) or dimeric nanodiscs (esdNDs) by controlling the oxidation/reduction conditions and lipid-to-protein ratios. When the esdNDs were used to prepare an antiviral nanoperforator that induced the disruption of the viral membrane upon contact, antiviral activity was dramatically increased, suggesting that the dimerization of nanodiscs led to cooperativity between linked nanodiscs. We expect that controllable structures, long-term stability, and aggregation resistance of esNDs will aid the development of novel versatile membrane-mimetic nanomaterials with flexible designs and improved therapeutic efficacy.

Original languageEnglish
Pages (from-to)36757-36768
Number of pages12
JournalACS applied materials & interfaces
Issue number31
StatePublished - 11 Aug 2021


  • end-spliced nanodisc
  • membrane scaffold protein
  • nanodisc
  • nanoperforator
  • protein trans-splicing


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