Oligonucleotide Molecular Sprinkler for Intracellular Detection and Spontaneous Regulation of mRNA for Theranostics of Scar Fibroblasts

Mengjia Zheng, Christian Wiraja, David C. Yeo, Hao Chang, Daniel Chin Shiuan Lio, Wei Shi, Kanyi Pu, Amy S. Paller, Chenjie Xu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Early diagnosis and timely intervention are key for the successful treatment of skin diseases like abnormal scars. This study introduces a nucleic-acid-based probe (i.e., molecular sprinkler) for the diagnosis and spontaneous regulation of the abnormal expression of fibrosis-related mRNA in scar-derived skin fibroblasts. Using mRNA encoding connective tissue growth factor (CTGF) as the model gene, a probe with three oligonucleotides is constructed, including a recognition sequence complementary to the CTGF mRNA, a siRNA against transforming growth factor receptor I (TGFβRI) as the CTGF mRNA suppressor, and a connecting sequence. The probe can detect CTGF mRNA with a limit of 10 × 10−9 m and distinguishes scar fibroblasts from normal ones in both 2D and 3D environments. Two days after transfection, the siRNA released from the probe reduces the expression of TGFβRI and, consequently, decreases the cellular expression of CTGF mRNA (up to 70%). This dual-role probe presents opportunities to monitor the TGF- β signaling pathway, screen for drugs that target the CTGF pathway, and determine the role of inhibition of the CTGF pathway in therapeutic efficacy.

Original languageEnglish (US)
Article number1802546
JournalSmall
Volume14
Issue number49
DOIs
StatePublished - Dec 6 2018

Keywords

  • abnormal fibroblast
  • mRNA
  • oligonucleotide sensors
  • skin disease

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

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