Polynucleotides: a clinician's guide

Polynucleotides (PNs) are highly purified, polymerised DNA fragments — most often derived from salmon or trout — injected into the skin to stimulate the body's own repair machinery. Unlike a dermal filler, they add little or no volume; instead they act as a biostimulator, improving skin quality, hydration, elasticity and tissue resilience over a course of treatments. They have become one of the fastest-growing regenerative options in aesthetic medicine, valued for a strong safety profile and their usefulness in delicate areas such as the under-eye.

What exactly are polynucleotides?

Polynucleotides are long chains of nucleotides — fragments of DNA — extracted and highly purified from the gonadal tissue of fish such as salmon or trout. During manufacture the DNA is fragmented, purified to remove proteins and other contaminants, and sterilised, which is what gives clinician-grade products their low immunogenicity and biocompatibility.

You will also see the term PDRN (polydeoxyribonucleotide), which refers to shorter DNA fragments from the same family. PN and PDRN are closely related and often discussed together; in practice, “polynucleotide” products for skin tend to be longer-chain polymers that form a soft, viscoelastic gel scaffold in the tissue. They are biodegradable and are broken down naturally over weeks to months. Importantly, polynucleotides are not hyaluronic acid, although some products combine the two.

How do polynucleotides work?

Polynucleotides are best understood as a biostimulatory, regenerative treatment rather than a volumising one. Several mechanisms are proposed in the literature:^1,2

• Fibroblast stimulation — PNs appear to encourage fibroblast activity and the production of collagen, elastin and extracellular matrix, improving skin firmness and quality over time.
• Adenosine (A2A) receptor activity — particularly attributed to PDRN, this is thought to drive an anti-inflammatory and pro-angiogenic effect, supporting tissue repair and microcirculation.
• The “salvage pathway” — the DNA fragments may supply nucleotides that cells reuse for their own turnover and repair.
• Hydration and scaffolding — the gel-like matrix holds water and provides a temporary scaffold, improving hydration and tissue quality.
• Antioxidant effect — a proposed free-radical scavenging action that helps protect against oxidative stress.

The net clinical effect is an improvement in the quality and resilience of the skin, which is why polynucleotides are often described as a “skin-quality” or “regenerative” treatment.

What can polynucleotides treat?

Polynucleotides are used across a range of skin-quality indications. Common applications include:

• Overall skin quality and radiance on the face — dullness, roughness and early laxity.
• The under-eye — one of the most popular uses, for skin quality, fine crepiness and the appearance of dark circles. Read our deeper guide on polynucleotides for the under-eye.
• Fine lines and early skin ageing, including “prejuvenation” in younger patients.
• Neck and décolletage, where skin is thin and volumising options are limited.
• Acne scarring and texture, and as part of a wider regenerative plan.
• As an adjunct to fillers, toxin and energy-based devices, to condition the skin around structural work.

How are polynucleotides different from fillers, skin boosters and exosomes?

It helps patients (and referrers) to understand where polynucleotides sit among the regenerative and injectable options:

• Dermal fillers (HA) add structural volume and lift. Polynucleotides do not — they improve the quality of the skin itself.
• Skin boosters (microdroplet hyaluronic acid) primarily hydrate. Polynucleotides hydrate and biostimulate, aiming at longer-term tissue change.
• Exosomes are cell-signalling vesicles — a newer, less standardised category. See our exosomes guide and our comparison, exosomes vs polynucleotides vs PRP.

What does the evidence say?

The evidence base for polynucleotides is growing but still maturing. Systematic and narrative reviews report improvements in skin elasticity, hydration and overall skin quality, alongside a favourable safety and tolerability profile.^1,2 PDRN in particular has a longer track record, including in wound healing. Emerging controlled studies — for example in dry, chapped lips — add to the picture.³

That said, many published studies are small, heterogeneous in protocol, and rely on subjective or short-term outcomes, so larger, well-designed randomised trials are still needed. The honest position to take with patients is that polynucleotides are a promising, well-tolerated regenerative option with encouraging but still-developing evidence — not a guaranteed or one-size-fits-all result.

What does a typical treatment course look like?

Protocols vary by product and indication, but a common approach is a course of two to four sessions spaced roughly two to four weeks apart, followed by maintenance every three to six months. Polynucleotides are injected intradermally or subdermally using a needle or cannula, with technique and depth tailored to the area. Downtime is usually minimal — some redness, swelling or small papules that settle within hours to a couple of days. For a worked example, see building a regenerative treatment plan around polynucleotides.

Who is suitable — and who isn't?

Polynucleotides suit patients with early-to-moderate skin-quality concerns, those wanting a regenerative rather than volumising result, and those seeking a gentle option for delicate areas. As with any injectable, careful patient selection and a full history are essential. Exercise caution or avoid treatment in:

• Known allergy to fish or seafood — products are highly purified, but caution is warranted and some manufacturers advise against use.
• Pregnancy and breastfeeding — insufficient safety data; generally avoided.
• Active infection, inflammation or broken skin at the treatment site.
• Autoimmune disease or immunosuppression — use clinical judgement.
• Bleeding disorders or anticoagulant therapy — higher bruising risk.

What results can patients expect?

Because polynucleotides work by stimulating the skin's own repair processes, results are gradual rather than instant. Patients typically notice improvements in skin quality, hydration and glow over several weeks as remodelling occurs, with the fullest effect after a completed course — often around four to twelve weeks. Results are not permanent, so maintenance sessions keep the effect going. Setting this expectation up front is key to satisfaction, especially for patients used to the immediate change of a filler.

How to choose a clinician-grade polynucleotide

Not all polynucleotide products are equal. When selecting a range, look at purity and concentration, the manufacturer's regulatory status (CE/UKCA) and clinical data, and the training and clinical support behind the brand. Our own research into how UK clinicians choose products found that clinical results, safety and regulatory approval consistently outrank price and marketing — a useful benchmark when building your tray. You can read more on our original research page.

At Harley Supplies we supply the Ameela polynucleotide range, a salmon-derived, highly purified line developed for skin rejuvenation:

Ameela® FaceMid-face & overall skin qualityAmeela® EyesDelicate under-eye skinAmeela® RejuvenationRegenerative skin quality

Frequently asked questions

This guide is intended for registered healthcare professionals. It summarises current evidence for educational purposes and is not a substitute for the product SPC/IFU, manufacturer training, or your own clinical judgement.

Written by

Dr Emmaline Ashley

Aesthetic Doctor · GMC 7582958 · COO of Harley Supplies

Dr Emmaline Ashley is an aesthetic doctor and published researcher in aesthetic medicine, with peer-reviewed work spanning product safety, regenerative treatments and medical education. She is a member of the Acquisition Aesthetics clinical faculty.

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