Inhibition of nuclease activity by a splice-switching oligonucleotide targeting deoxyribonuclease 1 mRNA prevents apoptosis progression and prolong viability of normal human CD4+ T-lymphocytes

Biochimie. 2020 Jul:174:34-43. doi: 10.1016/j.biochi.2020.04.009. Epub 2020 Apr 18.


The nuclease activity of deoxyribonuclease 1 (DNase I) is regulated by alternative splicing (AS) of its mRNA. The aim of this study was to define the ability of a splice-switching oligonucleotide (SSO) that base-paired with DNase I pre-mRNA to induce AS and inhibit nuclease activity in human T, B and NK lymphocytes. The SSO for DNase I could significantly downregulate the expression of full-length active DNase I and upregulate a truncated splice variant with a deleted exon 4. Such an induction of AS resulted in inhibition of nuclease activity and slowed apoptosis progression in anti-CD95/FAS stimulated lymphocytes. These results should facilitate further investigations of apoptosis regulation in lymphocytes and demonstrate that SSOs for DNase I are promising cytoprotective agents.

Keywords: Alternative splicing; Apoptosis progression; Deoxyribonuclease I; Lymphocytes; Splice-switching oligonucleotide.

MeSH terms

  • Adolescent
  • Adult
  • Alternative Splicing
  • Apoptosis*
  • Cell Survival
  • Deoxyribonuclease I / antagonists & inhibitors*
  • Deoxyribonuclease I / metabolism
  • Healthy Volunteers
  • Humans
  • Lymphocytes / cytology*
  • Lymphocytes / enzymology
  • Oligonucleotides / pharmacology*
  • RNA Precursors / metabolism
  • RNA, Messenger / metabolism
  • Young Adult


  • Oligonucleotides
  • RNA Precursors
  • RNA, Messenger
  • DNASE1 protein, human
  • Deoxyribonuclease I