ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Virology

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1600679

Transfection of unmodified oligodeoxynucleotide with polyethylenimine reduces the level of hepatitis B surface antigen

Provisionally accepted
Yu  Jun LinYu Jun Lin1Jing  LiJing Li2*
  • 1Research Center for Basic Medical Science, Qilu hospital of Shandong University, Jinan, China
  • 2Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China

The final, formatted version of the article will be published soon.

The delivery of nucleic acid into cells using polyethylenimine (PEI) as nonviral carrier is a potential candidate technique for the treatment of hepatitis B virus (HBV) infection. In the present study, PEI was used as cationic polymers and transfected with unmodified oligodeoxynucleotides in cell cultures and the BALB/c mouse model to investigate its efficiency in blocking HBV surface antigen (HBsAg) secretion. PEI/oligonucleotide complexes selectively inhibited HBsAg secretion in the culture supernatant, while there were no evident alterations in HBeAg and HBV DNA levels, thereby suggesting its potential inhibitory activity against the production of HBsAg.The complexes formed by PEI with double-stranded decoy oligonucleotides also suppressed HBsAg secretion but showed no expected interference with the intermediate levels of HBV transcription or replication. Furthermore, PEI/plasmid-DNA complexes demonstrated no influence on the expression levels of HBsAg, thus highlighting the specific effects of PEI/oligonucleotides exerted on HBsAg release. PEIoligonucleotides transfection prior to the viral inoculation impaired HBV infection in HepG2-NCTP cells. Importantly, the PEI/oligonucleotide complex also induced the decline of HBsAg in hydrodynamically injected BALB/c mice. These findings demonstrate that transfection of PEI/oligonucleotide complexes can help effectively reduce HBsAg level and may offer a new potential avenue for the development of anti-HBV treatment.

Keywords: Hepatitis B virus infection, Nonviral gene vector, unmodified oligonucleotide delivery, HBsAg secretion, anti-HBV treatment

Received: 26 Mar 2025; Accepted: 16 Apr 2025.

Copyright: © 2025 Lin and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jing Li, Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China

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