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

**Authors:** Junyu Lin, Jing Li

PMC · DOI: 10.3389/fmicb.2025.1600679 · Frontiers in Microbiology · 2025-05-01

## TL;DR

Using polyethylenimine with unmodified DNA reduces hepatitis B surface antigen in cells and mice, suggesting a new treatment approach.

## Contribution

Demonstrates that PEI/oligonucleotide complexes specifically inhibit HBsAg secretion without affecting other viral markers.

## Key findings

- PEI/oligonucleotide complexes reduced HBsAg in cell culture and mouse models.
- HBV infection was impaired in HepG2-NCTP cells with PEI/oligonucleotide transfection.
- HBsAg levels declined in mice treated with PEI/oligonucleotide complexes.

## Abstract

The delivery of nucleic acid into cells using polyethylenimine (PEI) as non-viral 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. PEI-oligonucleotides 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.

## Linked entities

- **Diseases:** hepatitis B (MONDO:0005344)

## Full-text entities

- **Genes:** Slc17a5 (solute carrier family 17 (anion/sugar transporter), member 5) [NCBI Gene 235504] {aka 4631416G20Rik, 4732491M05, AST, ISSD, NSD, SD}, HNF1A (HNF1 homeobox A) [NCBI Gene 6927] {aka HNF-1-alpha, HNF-1A, HNF1, HNF1alpha, IDDM20, LFB1}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, Gpt (glutamic pyruvic transaminase, soluble) [NCBI Gene 76282] {aka 1300007J06Rik, 2310022B03Rik, ALT, ALT1, Gpt-1, Gpt1}, CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385] {aka CREB, CREB-1}, KRT88P (keratin 88, pseudogene) [NCBI Gene 85348] {aka HBC, KRT122P, KRTHBP3}, SLC10A1 (solute carrier family 10 member 1) [NCBI Gene 6554] {aka FHCA2, NTCP}, SP1 (Sp1 transcription factor) [NCBI Gene 6667], CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}
- **Diseases:** infection (MESH:D007239), hepatocellular carcinoma (MESH:D006528), tumors (MESH:D009369), death (MESH:D003643), inflammation (MESH:D007249), hereditary diseases (MESH:D030342), liver cirrhosis (MESH:D008103), Chronic hepatitis B (MESH:D019694), Cytotoxicity (MESH:D064420), HBV infection (MESH:D006509), viral infections (MESH:D014777), liver damage (MESH:D056486), CMV (MESH:D003586)
- **Chemicals:** adenosine (MESH:D000241), NP-40 (MESH:C010615), DIG (MESH:D004076), phosphate (MESH:D010710), Trizol (MESH:C411644), C2 (MESH:C023714), CpG oligonucleotides (MESH:C408982), AC (MESH:D000186), 4',6-diamidino-2-phenylindole (MESH:C007293), polymer (MESH:D011108), MTT (MESH:C070243), PBS (MESH:D007854), PEI (MESH:D011094), nylon (MESH:D009757), DMSO (MESH:D004121), ammonium (MESH:D064751), Oligonucleotide (MESH:D009841), CCK-8 (MESH:D012844), sodium deoxycholate (MESH:D003840), Triton X-100 (MESH:D017830), eosin (MESH:D004801), paraformaldehyde (MESH:C003043), PEG 8000 (MESH:C000595216), nucleotide (MESH:D009711), formaldehyde (MESH:D005557), agarose (MESH:D012685), penicillin (MESH:D010406), water (MESH:D014867), NAPs (MESH:C043186), dON (MESH:C005914), H&amp;E (MESH:D006371), G418 (MESH:C010680), polyacrylamide (MESH:C016679), SDS (MESH:D012967), NaCl (MESH:D012965), lipid (MESH:D008055), CO (MESH:D002248), L-glutamine (MESH:D005973), puromycine (MESH:D011691), hematoxylin (MESH:D006416), glycerol (MESH:D005990), CO2 (MESH:D002245), FITC (-), streptomycin (MESH:D013307), Hoechst 33258 (MESH:D006690), paraffin (MESH:D010232)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Duck hepatitis B virus (no rank) [taxon 12639], Hepatitis B virus (no rank) [taxon 10407], Cytomegalovirus (genus) [taxon 10358], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), AD38 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_M177), HepG2.2.15 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_L855), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), /c — Mus musculus (Mouse), Hepatocellular carcinoma of the mouse, Cancer cell line (CVCL_9103), LD210-005 — Homo sapiens (Human), Plasma cell myeloma, Cancer cell line (CVCL_Y435)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12078216/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12078216/full.md

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Source: https://tomesphere.com/paper/PMC12078216