A few years ago, polynucleotides were almost exclusively discussed in aesthetic medicine circles. Clinicians in South Korea and Italy were injecting them into skin to accelerate wound healing and reduce the appearance of scars. Now the same ingredient is showing up in serums, eye creams, and face oils on retail shelves. The question worth asking is whether the topical version has any real relationship to the injectable one, or whether this is mostly marketing borrowing the credibility of a clinical procedure.
The honest answer is: it’s complicated, and the research is still catching up to the hype.
What PDRN and polynucleotides actually are
PDRN stands for polydeoxyribonucleotide. It is a fragment of DNA, specifically short chains of deoxyribonucleotides derived from salmon sperm (Oncorhynchus mykiss) or trout. This sounds alarming to some people, but the extraction process is highly purified and the resulting molecule has no biological identity linking it to its origin species. What remains are DNA fragments that the human body can actually recognise and use.
Polynucleotides is the broader category. PDRN is a type of polynucleotide, but the two terms get used interchangeably in marketing, which creates confusion. In clinical settings, the distinction matters because PDRN refers to a specific molecular weight range, roughly 50–1500 kDa, that has been most studied for tissue repair. In skincare products, you will often just see “polynucleotides” listed as the active, which may or may not be the same thing.
The mechanism that makes this ingredient interesting is its interaction with the A2A adenosine receptor. When PDRN binds to this receptor, it triggers a cascade that promotes fibroblast proliferation, stimulates collagen and elastin synthesis, and activates what researchers call the salvage pathway, which allows cells to recycle nucleotides for repair rather than synthesising them from scratch. A 2011 study published in the Journal of Plastic, Reconstructive and Aesthetic Surgery by Guizzardi et al. showed PDRN injections significantly increased VEGF (vascular endothelial growth factor) expression and accelerated tissue regeneration in wound models.
Why injections and topicals are not the same thing
This is where things get more complicated. The clinical evidence for injected polynucleotides is genuinely strong. Studies on intra-dermal injections show real improvements in skin hydration, elasticity, and texture, particularly in photoaged skin and under-eye hollowness. A randomised controlled trial published in the Journal of Cosmetic Dermatology in 2020 (Calzavara-Pinton et al.) found measurable improvements in skin roughness and elasticity after a series of PDRN injections compared to placebo.
Topical application is a different story. Polynucleotide molecules are large. High-molecular-weight fragments do not cross the stratum corneum to any meaningful depth under normal conditions. This is the same challenge that faces hyaluronic acid (Sodium Hyaluronate) when it comes in large molecular weights: it sits on the surface, which has some benefit for hydration but does not reach fibroblasts in the dermis.
Some formulators have responded to this by working with low-molecular-weight or fragmented polynucleotides, similar to how skincare uses hydrolysed versions of larger molecules. There is early in-vitro evidence suggesting smaller fragments can have some cellular signalling activity even at the surface level, but this is not the same as the dermal remodelling seen with injections. If a brand claims their serum replicates injectable results, that claim is not supported by current evidence.
What topical polynucleotides can reasonably do
This does not mean topical polynucleotides are useless. It means the realistic expectations need adjustment.
Surface-level hydration is one genuine benefit. Polynucleotides are hygroscopic, meaning they attract and hold water. Applied topically, they can function as a humectant, keeping the skin surface moist and temporarily plump. This is a real and useful effect, just not the structural remodelling that injections provide.
There is also growing interest in their antioxidant and anti-inflammatory properties at the skin surface. A 2022 paper in Molecules (Pavlou et al.) examined the free radical scavenging capacity of oligonucleotides and found moderate but consistent antioxidant activity in in-vitro models. This is relevant for skin exposed to UV and pollution, which describes most skin, most of the time.
Some researchers are also investigating whether topical polynucleotides can support the skin microbiome, since nucleotide fragments may act as a substrate for certain beneficial bacterial populations. This research is early and mostly speculative at this point, but it is an interesting direction.
How to read polynucleotide skincare products critically
A few things worth checking when you encounter a polynucleotide skincare product.
- Look for the concentration. Effective injectable formulations typically use 0.5–1.5% PDRN. Topical products rarely disclose this, which is itself informative.
- Check the molecular weight claim. If a brand specifies low-molecular-weight polynucleotides or hydrolysed DNA fragments, that is a more credible formulation claim than just listing “polynucleotides.”
- Be sceptical of before-and-after images that look identical to injectable treatment results. They almost certainly are from injectable treatments.
- Consider whether the product is positioned as a substitute for clinical treatment or a complement. The honest position is the latter.
The INCI name to look for on ingredient lists is Polydeoxyribonucleotide, sometimes listed as Sodium DNA or Hydrolyzed DNA. The salmon origin is sometimes noted parenthetically. There is no plant-derived equivalent that provides the same molecular structure, which creates a real challenge for brands committed to fully vegan formulations. This is a genuine limitation worth acknowledging rather than glossing over.
Where this ingredient fits in a natural skincare context
This is worth addressing directly, because polynucleotides occupy an unusual position in the natural beauty space. They are derived from a natural biological source (fish) and are not synthetically manufactured the way most pharmaceutical actives are. Yet they sit well outside the botanical ingredient world that most natural skincare brands work within.
At HOIA, where formulations are built on plant-based and naturally derived ingredients from places like Saaremaa, polynucleotides are not currently part of the product line. That is consistent with the brand’s focus on botanical actives and vegan formulations. The interest in polynucleotides from a natural skincare perspective is that they represent a shift in how the industry thinks about cellular communication and DNA-level signalling, even if the specific ingredient itself does not fit within a strictly plant-derived framework.
What this conversation does highlight is the value of ingredients that work at the level of cellular repair rather than surface coverage. Ingredients like Sodium Hyaluronate, plant-derived peptides, and certain Nordic botanicals such as sea buckthorn (Hippophae rhamnoides) and cloudberry (Rubus chamaemorus) activate skin repair pathways through different mechanisms. They are not the same as PDRN, but they are part of the same broader thinking about supporting skin biology rather than just covering it.
The practical takeaway
If you are considering a polynucleotide skincare product, expect hydration support and potentially some surface-level antioxidant benefit. Do not expect the structural collagen remodelling seen in clinical injectable protocols. That gap between expectation and reality is where most of the disappointment with this ingredient comes from.
If you have access to a qualified aesthetic physician and are interested in PDRN treatments for specific concerns like under-eye crepiness, acne scarring, or significant photoaging, the evidence for injectable protocols is solid enough to warrant a real consultation. That is a different product category and a different conversation.
For everyday skincare, the more honest approach is to use well-formulated products with ingredients whose topical efficacy is well documented and to treat clinical procedures as clinical procedures rather than something a serum can replicate. If a brand is trying hard to convince you otherwise, that is a reason to slow down, not speed up.