Nucleic Acid Technologies in Skin Science: From PDRN to Precision RNA Actives
Hang Ma, Ph.D.,
Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, USA
In my laboratory, nucleic acids are everyday tools. We design them to silence genes, modulate pathways, and dissect mechanisms of skin biology. In academic research, RNA interference (RNAi) and gene regulation are standard approaches to understanding how cells function (Table 1).
Yet when I step into conversations within the cosmetic and personal care industry, I am reminded that translating those tools into real-world products is far more complex.
The rising visibility of PDRN in aesthetic dermatology has brought nucleic acid–derived materials into the mainstream skin discussion. But from a research perspective, PDRN is less a final destination and more a starting point. It signals that cosmetic science is beginning to intersect more deeply with molecular biology.
The important question is not whether nucleic acids can influence skin biology. They can, we already know. The question is how responsibly and realistically this technology can be translated into cosmetic innovation.
Table 1. Major Classes of Nucleic Acid–Based Technologies Relevant to Skin Science
| Class of Nucleic Acid | Structural Feature | Biological Skin Functions (Research Context) | Potential Skincare Applications (Cosmetic Context) |
| Polydeoxyribonucleotide (PDRN) | Mixture of DNA fragments (typically 50–2000 bp), derived from salmon DNA | Activates adenosine A2A receptor; supports angiogenesis; modulates inflammation; provides nucleotide substrates for repair | Supports visible skin recovery; enhances post-procedure appearance; promotes the look of revitalized skin |
| Small Interfering RNA (siRNA) | Short double-stranded RNA (~21–23 nucleotides) designed to match specific mRNA sequences | Sequence-specific gene silencing via RNA interference; reduces expression of targeted proteins | Precision modulation of pigmentation-related pathways; targeting enzymes involved in visible aging (pending delivery feasibility) |
| Antisense Oligonucleotides (ASOs) | Single-stranded synthetic DNA or RNA (~15–25 nucleotides) complementary to target mRNA | Blocks translation or promotes degradation of specific mRNA transcripts | Selective downregulation of inflammatory mediators or matrix-degrading enzymes (conceptual cosmetic adaptation) |
| MicroRNA (miRNA) Modulators | Small non-coding RNA regulators (~22 nucleotides) or mimics/inhibitors thereof | Fine-tune gene networks; regulate cell differentiation, inflammation, and stress responses | Balancing visible skin tone; supporting skin resilience and barrier-related gene networks |
| DNA Aptamers | Short, structured single-stranded DNA or RNA sequences with defined 3D folding | Bind selectively to specific proteins (antibody-like recognition without immunogenicity) | Targeted delivery systems; precision binding to surface proteins for advanced active targeting strategies |
| mRNA-Based Systems (primarily therapeutic research stage) | Single-stranded messenger RNA encoding specific proteins | Directs the synthesis of specific proteins within cells | Currently outside the cosmetic scope; informs future delivery and stability technologies |
PDRN: A Gateway Ingredient
Polydeoxyribonucleotide (PDRN; typically derived from salmon sperm DNA) is now used in regenerative dermatology to support wound healing and post-procedure recovery. Mechanistically, it acts primarily through activation of the adenosine A2A receptor, promoting angiogenesis and modulating inflammation [1,2]. It may also provide nucleotide substrates that support cellular repair.
From a molecular standpoint, PDRN is indirect. It does not silence specific genes or precisely regulate transcription. Instead, as a heterogeneous mixture of relatively long double-stranded DNA fragments, it broadly supports regenerative pathways. In contrast, newer nucleic acid technologies such as siRNA, antisense oligonucleotides, and microRNA modulators are chemically defined, short, sequence-specific single- or double-stranded oligonucleotides designed to bind complementary RNA targets and modulate gene expression with high precision (Figure 1).
However, its commercial and clinical success accomplished something important: it demonstrated that nucleic acid–derived materials could be safe, manufacturable, and accepted in aesthetic applications.
That acceptance opens the door to deeper discussions about more targeted nucleic acid technologies.
Figure 1. PDRN vs. RNA-Based nucleic acid technologies. Left: PDRN consists of longer, non-sequence-specific DNA fragments (commonly salmon sperm-derived) that broadly support regenerative pathways. Right: RNA-based technologies such as ASOs, siRNA, and mRNA are shorter, sequence-defined molecules designed to bind specific RNA targets and modulate gene expression with precision.
What We Do in the Lab
In academic research, we use nucleic acids with much greater specificity.
Small interfering RNA (siRNA), antisense oligonucleotides, and microRNA modulators allow us to selectively reduce the expression of individual genes of our interest. If we want to investigate a collagen-degrading enzyme, we silence it. If we want to explore pigmentation regulation, we downregulate a melanogenic regulator and observe the cellular response. This precision allows us to move beyond general stimulation or inhibition (often by small molecules, i.e., medicines or natural products) and directly interrogate causal mechanisms. In skin biology research, we use RNA-based approaches to study molecular events, including the regulation of melanogenesis, inflammatory mediation, remodeling of extracellular matrix, and responses to oxidative stress. From a scientific perspective, the level of control is remarkable. But this is where the translational gap becomes clear.
The Translational Gap
In the laboratory, delivery systems are optimized for experimental conditions. We use transfection reagents or other tools that are not used in finished cosmetic formulations.
The skin barrier adds another layer of complexity. Nucleic acids are macromolecules with a negative charge that are vulnerable to enzymatic degradation. The stratum corneum is highly effective at preventing their penetration.
Even if gene modulation works reliably in vitro, ensuring stability, bioavailability, and reproducibility in a topical product is an entirely different challenge.
Emerging delivery systems, such as lipid nanoparticles, polymer complexes, liposomal encapsulation, and vesicular platforms, offer promising strategies [3]. Advances in nanoparticle engineering, highlighted by therapeutic mRNA technologies, demonstrate that nucleic acids can be stabilized and delivered effectively in biological systems [4].
However, several challenges in cosmetic applications must be addressed. These include their long-term stability in emulsions, compatibility with preservatives, cost scalability, safety expectations, and (most likely) regulatory classification and claims. Scientific feasibility does not automatically equal commercial viability. Bridging that gap requires interdisciplinary collaboration.
Cosmetic Science Is Evolving Too
Cosmetic science today looks very different from what it did even a decade ago. Like many life sciences, it is becoming faster, more data-driven, and more interdisciplinary.
Artificial intelligence (AI) is now used to screen bioactive compounds, predict structure-function relationships, analyze omics datasets, and accelerate formulation development [5]. Computational tools can identify molecular targets in weeks (or shorter!) rather than years. Data integration platforms allow us to connect transcriptomics, proteomics, and clinical observations more efficiently than ever before. This acceleration creates opportunity, but it also creates risk. In a fast-paced innovation environment, there is a temptation to chase the NBT (‘next big thing’) concepts before foundational evidence is fully established. Nucleic acid technologies are inherently compelling. They sound advanced. They signal biotech sophistication. But more than ever, cosmetic innovation must be evidence-based.
Precision technologies demand precision validation. Mechanistic claims must be supported by robust data. Delivery systems must be characterized, not assumed. Safety profiles must be rigorously evaluated. Trendy ideas may generate excitement, but only reproducible science sustains long-term credibility.
Regulatory and Practical Realities
From an academic standpoint, modulating gene expression is a research objective. From a regulatory standpoint, it can be a classification issue. Sequence-specific gene silencing may cross boundaries depending on jurisdiction and the specific wording of claims. Clear positioning is essential to remain within cosmetic definitions. Responsible translation requires early dialogue between researchers, formulators, regulatory experts, and marketers. Scientific elegance must align with regulatory clarity and consumer transparency.
Bridging Discovery and Application
As a university researcher, what excites me most about nucleic acid technologies is not simply their precision. It is the opportunity they create for stronger collaboration between academia and industry.
Academic labs can identify and validate molecular targets. Industry partners can translate those insights into stable, safe, and scalable formulations. AI and computational biology can accelerate discovery, but careful experimental validation must anchor development.
PDRN demonstrated that nucleic acid–derived materials could enter aesthetic practice. RNA-based precision technologies represent the next scientific frontier. Whether they become routine cosmetic ingredients will depend not on novelty alone, but on rigorous evidence, thoughtful delivery design, and responsible positioning.
Cosmetic science is evolving rapidly, alongside other life sciences. As new tools emerge, from RNA technologies to AI-driven discovery platforms, the pace of innovation will continue to accelerate. In this environment, our responsibility as scientists is clear.
Innovation should not be driven by trends, but by data.
And the future of nucleic acid technologies in skin care will be shaped not by how advanced they sound, but by how convincingly they are supported.
References
[1] Colangelo, Maria Teresa, Carlo Galli, and Stefano Guizzardi. “Polydeoxyribonucleotide regulation of inflammation.” Advances in Wound Care 9.10 (2020): 576-589.
[2] Colangelo, Maria T., Carlo Galli, and Stefano Guizzardi. “The effects of polydeoxyribonucleotide on wound healing and tissue regeneration: a systematic review of the literature.” Regenerative Medicine 15.6 (2020): 1801-1821.
[3] Mendes, Bárbara B., et al. “Nanodelivery of nucleic acids.” Nature Reviews Methods Primers 2.1 (2022): 24.
[4] Qin, Ming, Guangsheng Du, and Xun Sun. “Recent advances in the noninvasive delivery of mRNA.” Accounts of Chemical Research 54.23 (2021): 4262-4271.
[5] Eppler, Angela R., and Hang Ma. “Artificial Intelligence Beauty Revolution—State of the Art and New Trends from the SCC78 Annual Meeting.” Cosmetics 12.2 (2025): 73.