How do polynucleotides work?

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Polynucleotides are fragments of purified DNA suspended in a gel. Once injected, they are thought to act in two ways: physically, as a water-holding scaffold in the skin, and biologically, by influencing the cells that maintain and repair skin tissue. Both ideas are plausible and supported by laboratory work, but the clinical evidence in humans is still limited.

What polynucleotides are made from

The raw material is DNA extracted from the milt of salmon or trout. This source is used because fish DNA is highly compatible with human DNA at the molecular level and is available in large, consistent quantities.

Manufacturing involves extraction, filtration, sterilisation and purification steps designed to remove proteins, peptides and other fish material, leaving chains of nucleotides of a controlled length. What remains is not functional genetic material: the chains are too short and fragmented to carry meaningful genetic information.

Products differ in molecular weight, concentration and whether the polynucleotides are combined with other ingredients such as hyaluronic acid. Those differences affect how a product feels on injection and where a practitioner might choose to use it.

The proposed mechanism

A hydrating scaffold. Polynucleotide chains bind water and form a temporary three-dimensional mesh in the dermis. This is thought to improve hydration and give cells a structure to move and organise along, in much the same way a trellis supports a plant.

A signal to fibroblasts. Fibroblasts are the cells that produce collagen and elastin. Laboratory and animal studies suggest that polydeoxyribonucleotide (PDRN), a closely related material, can stimulate fibroblast activity, partly through adenosine A2A receptors, and can support the “salvage pathway” that recycles nucleotides for new cell building.

Modulating inflammation. The same research suggests a dampening effect on inflammatory signalling and a supportive effect on local blood supply, which is why the material has also been studied in wound healing and tendon injury outside cosmetic medicine.

Note the important distinction: much of this mechanistic work concerns PDRN in laboratory models, not cosmetic polynucleotide products in human faces. Mechanism explains why a treatment might work; it is not evidence that it does.

What the evidence shows

Published clinical studies on cosmetic polynucleotide injections generally report modest improvements in skin hydration, elasticity and roughness, and improvements in under-eye appearance, assessed a few weeks to a few months after a short course. Tolerability in these studies is usually good, with mild, short-lived local reactions.

Limitations are consistent across the literature: small numbers of participants, short follow-up, few or no control groups, outcomes rated by the treating clinician, and frequent involvement of manufacturers. Independent, adequately powered, randomised trials are scarce.

A fair summary is that polynucleotides are a plausible, generally well-tolerated treatment with early supportive evidence, not an established one with proven long-term benefit.

How long the effect lasts

The injected material itself is broken down by the body over a matter of weeks. Any lasting effect therefore depends on the changes it prompts in the skin, rather than on the product remaining in place.

Clinics commonly describe results building over one to three months after a course and gradually fading over six to twelve months, with maintenance sessions offered thereafter. Those timeframes reflect clinical practice and marketing rather than strong trial data, and individual responses vary widely. See how many sessions for typical treatment plans.

Limitations and open questions

  • There is no agreed standard dose, injection depth or session interval across brands.
  • It is unclear whether differences between brands translate into differences in outcome.
  • Long-term safety and effectiveness beyond a year or two are not well documented.
  • Most studies measure surrogate outcomes such as skin elasticity readings rather than what patients themselves notice.
  • Comparative trials against hyaluronic acid skin boosters are rare, so claims that one is superior should be treated cautiously.

Sources

  • Squadrito F et al. Pharmacological activity and clinical use of PDRN (peer-reviewed review of polydeoxyribonucleotide mechanisms)
  • Colangelo MT et al. Polydeoxyribonucleotide in tissue regeneration: a narrative review of the literature
  • Cavallini M et al. Consensus and clinical reports on polynucleotide injection in aesthetic dermatology
  • MHRA — guidance on medical devices regulation in Great Britain