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Cell penetrable peptide nucleic acids targeting PDZK1IP1 with anti-inflammatory potential in human keratinocytes

Daram Jung1, Sun Hee Jin2, Yeasel Jeon3

  • 1Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea; OliPass Corporation, Yongin, Gyeonggi 17015, Republic of Korea.

Bioorganic & Medicinal Chemistry Letters
|November 18, 2024
PubMed

Insights

Modified peptide nucleic acids (PNAs) effectively suppressed PDZK1IP1 gene expression, reducing inflammation in skin cells. This offers a promising therapeutic strategy for inflammatory skin diseases.

Area of Science:

  • Molecular biology
  • Dermatology
  • Oligonucleotide therapeutics

Background:

  • PDZK1-interacting protein 1 (PDZK1IP1) is implicated in skin inflammatory diseases and epithelial tumors.
  • Peptide nucleic acids (PNAs) are known for their high binding affinity and nuclease resistance, making them suitable for therapeutic applications.

Purpose of the Study:

  • To investigate the modulation of PDZK1IP1 gene expression using modified PNAs.
  • To assess the therapeutic potential of PNAs targeting PDZK1IP1 in skin inflammatory conditions.

Main Methods:

  • Synthesis of modified PNA oligomers with enhanced water solubility and cellular permeability via conjugation with primary amine chains.
  • Evaluation of cellular permeability of fluorescein-labeled modified PNAs in HaCaT cells.
  • Assessment of PDZK1IP1 gene expression suppression and alleviation of interferon γ (IFNγ)-induced inflammatory responses in normal human keratinocytes.

Main Results:

  • Modified PNA oligomers demonstrated significantly enhanced cellular permeability in HaCaT cells compared to unmodified PNAs.
  • The modified PNAs effectively suppressed PDZK1IP1 gene expression.
  • Interferon γ (IFNγ)-induced inflammatory responses in normal human keratinocytes were alleviated by the modified PNAs.

Conclusions:

  • Modified PNAs targeting PDZK1IP1 show potential for treating skin inflammatory diseases.
  • Enhanced PNA design improves cellular uptake and therapeutic efficacy.
  • PDZK1IP1 represents a viable therapeutic target for dermatological conditions.
Keywords:
Anti-sense oligonucleotideCell penetrationPDZK1IP1Peptide nucleic acidsSkin inflammation

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