Polynucleotides and PDRN: what “salmon DNA” really shows in the skin

What you inject when you inject “salmon DNA”

Two different families are sold under the “salmon DNA” label. PDRN (polydeoxyribonucleotide) consists of relatively short DNA fragments; PN (polynucleotides) of longer, higher-molecular-weight chains³. Both come mainly from the sperm of Oncorhynchus mykiss (rainbow or “salmon” trout) and Oncorhynchus keta (chum salmon)³¹⁴. A 2021 review describes PDRNs as a family of DNA-derived drugs with molecular weights from 50 to 1500 kDa¹⁴.

The problem for physicians is that the boundary is not standardized. A 2025 review notes that no standardized molecular-weight criteria separate PN from PDRN, that these distinctions are often defined by manufacturers using proprietary technologies, and that fine control of fragment size is difficult, producing heterogeneity³. In other words: “PN” in two different brands does not guarantee the same material.

PDRN was not born in aesthetics. A 1996 paper describes it as the active ingredient in a new formulation of the drug Placentex, then obtained from human placenta, with fragments of 50 to 2000 base pairs¹². Production later moved to trout: in 2018 a Korean study described O. mykiss-derived Placentex as the product “currently used in the clinic” and compared it with an O. keta PDRN in mice¹³.

The mechanism: the A2A receptor and a matrix scaffold

For PDRN, the best-described proposed mechanism is selective activation of the adenosine A2A receptor, with anti-inflammatory effects mediated, per Kim's review, by increased VEGF and interleukin-10, plus nucleotide supply to the salvage pathway³. A 2017 review of 29 studies reached the same conclusion about A2A, but also noted wide dose variability outside the skin¹⁵.

PN, with its longer chains, is mainly credited with a role in extracellular-matrix remodeling³. That is a reasonable hypothesis, but much of the reasoning comes from in vitro and animal models; what matters to the clinician is how much of it translates into measured clinical outcomes.

What the systematic reviews say

The PROSPERO-registered systematic review by Lampridou and colleagues (2025) included 9 studies of low and moderate quality with 219 PN-treated patients¹. It describes improvements in wrinkles, texture and elasticity, statistically significant in several studies, generally mild and transient side effects, and wide variation in injection areas and techniques¹. Two of its four authors declared industry ties: one sits on the R&D steering board of PN manufacturer Mastelli Srl, another is a trainer for a distributor of those products¹.

A July 2026 review restricted to randomized trials found 7 trials with 183 participants: four on rejuvenation, one on scar prevention and two on wound healing². The most consistent benefits appeared in wounds, not aesthetics, and the authors flag small samples, heterogeneous protocols and disparate outcome measures².

Around the eyes, a 2026 review concludes that hyaluronic acid remains superior for structural correction and that PN shows improvements in elasticity, hydration and fine lines, but that heterogeneity prevents definitive conclusions⁴. Lee's Korean split-face trial (27 subjects) illustrates the nuance: against a non-crosslinked hyaluronic acid, global improvement scales did not differ; elasticity, hydration, roughness and pore volume improved more on the PN side¹⁶.

The Italian trials are equally small. In acne scars, Araco compared PN with saline in 20 women (10 per group) and only the PN group improved from baseline¹⁷. In nasolabial folds, the same group treated 20 women in a split-face design and called it an exploratory study¹⁸. A 2026 observational study of 66 patients, whose publication costs Mastelli covered, reported favorable real-world results without a control group²⁰.

Two retracted trials

The phase III trial by Pak and colleagues (2014) compared Rejuran with a hyaluronic acid filler for crow's feet in 72 patients; primary and secondary efficacy outcomes showed no significant difference between groups⁷. The paper stated that no author had financial ties to industry⁷. In 2016 the journal retracted it: according to the notice, trial expenses were paid by the filler's manufacturer, a co-author worked at its R&D center, and the editorial board deemed it a publication impaired by incorrect disclosure of conflicts of interest and funding⁸.

The second case is more recent. A 2025 Korean trial of 218 participants compared a polycaprolactone filler with Rejuran for crow's feet⁵. In 2026 it was retracted at the authors' request: the comparator had been described as pegylated polycaprolactone when it was pure polycaprolactone, an error that, per the notice, undermines the reliability of the findings⁶. The problem was not in the PN arm, but the study can no longer be cited as evidence.

Reviews are not immune either: a 2024 paper proposing definitions and classifications of “skin boosters” was retracted in 2025 over an insufficient peer-review process and images taken from the internet or prior literature without proper citation; the corresponding author disagreed with the retraction⁹¹⁰. Before citing a study in this field, check its status on PubMed.

Regulation: a device in Europe and Korea, not approved in the US

In South Korea, according to Kim's review, PN injectables are regulated as medical devices (e.g., Rejuran) and PDRN as a prescription medicine (e.g., Placentex)³. In the European Union, Mastelli's PN marketed as Plinest is described in the literature as a class III CE-marked medical device²⁰.

In the United States, the FDA regulates dermal fillers as medical device implants, tells consumers not to buy fillers online and warns of counterfeit or unapproved products; its filler page does not mention polynucleotides²¹. Our openFDA search returned no record for PN, PDRN, Rejuran or Plinest²². The Korean daily EDAILY reported in August 2026 that PharmaResearch, Rejuran's manufacturer, estimates US market entry around 2031–2032, that there is no precedent for an FDA-approved PN skin booster, and that industry sources do not rule out the FDA treating it as a drug, with added immunogenicity and batch-consistency demands²³.

Profhilo offers the contrast: it is not PN but a hyaluronic acid formulation, available in more than 70 countries, and in July 2026 Evolus announced a deal with IBSA to develop it and seek US approval²⁴.

And in Panama?

The Ministry of Health has a National Directorate of Medical Devices; a 2020 report from that directorate stated that implementing device sanitary registration depended on amending Laws 90 of 2017 and 92 of 2019²⁵. We found no public search tool for device registrations that would let us verify whether a specific PN or PDRN product is registered in the country, so we can neither confirm nor rule out its status.

Useful questions before choosing a product

• Which species does the DNA come from, and what fragment-size range does the manufacturer declare?³¹⁴
• Are there trials with this product, or only with the “PN” class? One brand's results do not automatically transfer to another³.
• What is its regulatory status in its home market (class III CE device; device or drug in Korea)?³²⁰
• Are any of the studies cited in the marketing material retracted?⁶⁸¹⁰