RNA Aptamer Delivery through Intact Human Skin.

Area of Science:

• Biochemistry
• Dermatology
• Drug Delivery

Background:

• Conventional drug delivery limits therapeutic molecule size to <500 Da for skin penetration.
• The stratum corneum presents a significant barrier to topical drug absorption.
• Large molecules like RNA are generally not considered candidates for transdermal drug delivery.

Purpose of the Study:

• To challenge the conventional understanding of skin penetration limitations for large molecules.
• To investigate the transdermal delivery of a large RNA aptamer targeting IL-23.
• To assess the therapeutic potential of RNA aptamers delivered topically to the skin.

Main Methods:

• Utilized a 62-nucleotide (20,395 Da) RNA aptamer specific to human IL-23.
• Demonstrated aptamer skin penetration using fluorescent labels and dual hybridization assays.
• Assessed aptamer integrity and biological activity in ex vivo human skin models.
• Measured changes in cytokine mRNA and protein levels following aptamer treatment.

Main Results:

• Confirmed penetration of the large RNA aptamer into both epidermis and dermis of human skin.
• Quantified aptamer levels exceeding therapeutic concentrations by over 100,000-fold.
• Demonstrated that the aptamer retains its functional structure and biological activity post-penetration.
• Showed topical aptamer application reduced IL-17f and IL-22 levels by ~45% in stimulated skin.

Conclusions:

• Very-large-molecular-weight RNA aptamers can permeate the intact human skin barrier.
• Therapeutically relevant concentrations of functional RNA aptamers can be achieved in the epidermis and dermis.
• This study opens new avenues for topical RNA-based therapeutics targeting skin conditions.