Topical ionic liquid-mediated GLUT1 gene editing ameliorates psoriasis and prevents recurrence

Area of Science:

• Dermatology
• Immunology
• Gene Therapy

Background:

• Psoriasis is a chronic inflammatory skin disease with immune dysregulation and frequent relapses.
• Current treatments for psoriasis often fail to achieve lasting remission.
• Overexpression of glucose transporter 1 (GLUT1) in keratinocytes drives inflammation and immune imbalance in psoriasis.

Purpose of the Study:

• To develop a composite ionic liquid-mediated transdermal platform for CRISPR-Cas9 ribonucleoprotein (CIL-RNP) delivery.
• To achieve efficient GLUT1 gene editing in keratinocytes for psoriasis treatment.
• To evaluate the therapeutic efficacy of CIL-RNP in a psoriasis mouse model.

Main Methods:

• Development of a composite ionic liquid-mediated transdermal platform for CIL-RNP delivery.
• In vitro assessment of CIL-RNP efficiency in gene editing, PKM expression, and cytokine secretion.
• In vivo evaluation of CIL-RNP topical administration in a psoriasis mouse model, assessing lesion severity, immune cell profiles, and relapse risk.

Main Results:

• CIL-RNP achieved 76.6% editing efficiency, downregulating PKM and reducing inflammatory cytokines.
• Topical CIL-RNP significantly decreased psoriasis lesion severity (50% PASI score reduction) in mice.
• Treatment modulated immune responses by inhibiting M1 macrophage polarization, reducing ROS, rebalancing Th17/Tregs, and diminishing TRMs.

Conclusions:

• Ionic liquid-based CRISPR-RNP transdermal editing of GLUT1 is a novel and effective strategy for psoriasis.
• This approach restores immune homeostasis and has potential for long-term remission.
• The strategy may have broader applications for other cutaneous immunopathological conditions.