Summary
- PN and PDRN are both extracted from salmon DNA; they differ in chain length. A 2025 paper proposed 1,500 kDa as the dividing line: chains longer than this are called PN, shorter ones PDRN.
- Long chains (HMW) hold more water, are more viscous, form a mesh-like scaffold and break down more slowly. Short chains (LMW) spread easily and stimulate cells more quickly.
- The “optimal” size is not a straight line. In a rat wound study, the mid-range (50–1,500 kDa) gave better wound quality than either very short or very long chains.
- No human study has yet compared high and low molecular weight PN head to head. In practice, the choice is based on physical properties, treatment area and skin thickness.
What are PN and PDRN?
Both are long-chain DNA extracted and purified from the germ cells of salmon or trout. Fish DNA is structurally similar to human DNA, so it is well tolerated by the body.8 The terms PN and PDRN have long been used interchangeably, so Laurent and colleagues proposed the following criteria in Biomolecules in 2025:1
| PDRN | PN | |
|---|---|---|
| Molecular weight | Below 1,500 kDa (originally defined as about 50–1,500 kDa) | 1,500 kDa and above; reported up to about 8,000 kDa |
| Form | Clear liquid that spreads easily | Viscous gel that forms a mesh-like scaffold in the skin |
| Described strengths | Stimulates cells via the adenosine A2A receptor | Holds water, supports the skin and gradually releases shorter chains |
On the market, “high molecular weight (HMW) PN” and “low molecular weight (LMW)” refer to positions on this same scale. Each brand defines its own numbers, and most do not disclose measured values.
What molecular size changes
1. Hydration
Long DNA chains bind more water than short ones. Laurent and colleagues concluded that PN has “superior properties” for restoring skin hydration.1 This is why skin often looks more dewy soon after a gel-type PN treatment.
2. Scaffold in the skin
3-D scanning electron microscopy of gel-type PN shows a regular polygonal structure of about 1–7 micrometres.5 This scaffold gives cells something to anchor to as they build tissue, which liquid PDRN does not provide.
3. Time in the skin
PN gel breaks down more slowly than liquid PDRN.1 As it slowly degrades, it gradually releases water and shorter DNA fragments.6 Put simply, high molecular weight PN acts like a “reservoir” that turns into low molecular weight fragments in the skin over time.
4. Cell stimulation
The most studied mechanism is that the digested DNA fragments bind the adenosine A2A receptors on fibroblasts, which reduces inflammation and promotes cell migration and tissue formation, together with the recycling of nucleotides to build new DNA (the salvage pathway).18 Short chains reach this mechanism more quickly.
Is a smaller molecule better?
The answer is “it depends on what you measure”, and the evidence points in different directions.
- In the lab, a 2025 study cut plant-derived DNA into different sizes and found that the smallest fragments (under 200 base pairs) increased skin cell proliferation the most, to about 125–130% of the control, and increased cell migration speed 1.8–2-fold.3 However, this was plant DNA tested in culture dishes, not human skin.
- In animals, Hwang and colleagues (2018) compared 3 sizes in rat wounds: below 50 kDa, 50–1,500 kDa and above 1,500 kDa. Wounds closed at a similar rate in all groups, but the mid-size group had more collagen and less fat accumulation in the wound.2
The most accurate conclusion for now is that size does matter, but it is neither “the smaller the better” nor “the bigger the better”. Each size range has different strengths.
What is still unproven
- No human study has directly compared HMW and LMW. Most clinical PN studies have no control group, for example a study of 30 people with Asian skin who received 3 treatments 4 weeks apart.6
- Many studies did not actually measure molecular size. A 2025 review pointed out that most studies quote a size range without confirming it by methods such as gel electrophoresis or HPLC.4
- Standards are not yet aligned. A 2026 review concluded that the evidence is still “heterogeneous” and that more controlled studies are needed on dosing, injection technique and safety reporting.8
- Read the research carefully. At least one PN paper published in the Journal of Cosmetic Dermatology in 2022 was later retracted.9 When citing research, it is worth checking the paper's status.
So if someone tells you one brand “works better” because its molecules are bigger or smaller, ask whether there is a human study comparing them. For now, the answer is mostly no.
How we choose in clinic
Without head-to-head evidence, the choice is based on the product's physical properties and the skin concern in each area. This section describes the approach we use at Vinfinity Clinic.
| Situation | Approach | Rationale |
|---|---|---|
| Dehydrated, dull or thin skin across the face | Gel-type PN injected into the dermis | Holds water, supports the skin, lasts longer |
| Thin, crêpey or dark under-eye skin | A product designed for the eye area, injected as very small droplets with a fine needle | Thin skin needs a product that spreads easily, lowering the chance of bumps |
| Irritated skin, or recovery after laser or other procedures | A fast-spreading formulation | Focus on calming inflammation and short-term repair |
| Sagging skin with loss of structure | PN alone is not enough; it usually needs to be combined with structural support or collagen stimulation | PN improves skin quality; it does not lift or add structure |
One example is the product we use at the clinic, which comes in two formulations with the same concentration of 20 mg/mL but different treatment areas: the eye-area formula is injected superficially with a 34G needle, while the full-face formula is injected deeper with a cannula.10 In other words, concentration alone does not tell you whether a formulation is suitable.
A 2026 clinical perspectives paper recommends intradermal injection of 0.02–0.04 mL per point, 3–5 mm apart, for 3 sessions 4 weeks apart. The authors themselves note that this guidance is based mainly on clinical experience.7
At Vinfinity, we use PN as layer 1, “repairing the foundation”, in our layered approach to skin, together with hydration, structural support and refining details. Read more in our article on layered injection and on the skin booster page.
Safety
- Common side effects are local, such as raised bumps at injection points, redness and bruising, which settle on their own within a few days.8
- If you are allergic to fish or fish products, tell your doctor beforehand, although not everyone with a fish allergy will react.8
- Some products also contain hyaluronic acid. You should know every ingredient in what is being injected.
- Do not have injections while there is an infection in the treatment area, or during pregnancy or breastfeeding.
Questions to ask your doctor before PN injections
- What is the product called, is it registered with the Thai FDA, and can I see the box?
- Is it a gel (high molecular weight) or liquid (low molecular weight) type, and why was it chosen for my skin?
- Does it contain anything other than PN?
- How many sessions will I need, how far apart, and how will results be measured?
References
- Laurent A, et al. From Polydeoxyribonucleotides (PDRNs) to Polynucleotides (PNs): Bridging the Gap Between Scientific Definitions, Molecular Insights, and Clinical Applications of Multifunctional Biomolecules. Biomolecules. 2025;15(1):148. doi:10.3390/biom15010148
- Hwang KH, Kim JH, Park EY, Cha SK. An effective range of polydeoxyribonucleotides is critical for wound healing quality. Molecular Medicine Reports. 2018;18:5166–5172. doi:10.3892/mmr.2018.9539
- An CE, Bak SU, Jung MS, Kim DJ, Jin HU, Lee SY. Anti-Aging Efficacy of Low-Molecular-Weight Polydeoxyribonucleotide Derived from Paeonia lactiflora. International Journal of Molecular Sciences. 2025;27(1):220. doi:10.3390/ijms27010220
- Polydeoxyribonucleotides as Emerging Therapeutics for Skin Diseases: Clinical Applications, Pharmacological Effects, Molecular Mechanisms, and Potential Modes of Action. Applied Sciences. 2025;15(19):10437. doi:10.3390/app151910437
- Kim et al. High-resolution 3-D scanning electron microscopy (SEM) images of DOT polynucleotides (PN): Unique scaffold characteristics and potential applications in biomedicine. Skin Research and Technology. 2024;30:e13667. doi:10.1111/srt.13667
- Lim TS, Liew S, Tee XJ, Chong I, Lo FJ, Ho MJ, Ong KT, Cavallini M. Polynucleotides HPT for Asian Skin Regeneration and Rejuvenation. Clinical, Cosmetic and Investigational Dermatology. 2024;17:417–431. doi:10.2147/CCID.S437942
- Rho NK, Chilukuri S, Chan G, Kim MJ, Shin J, Suwanchinda A. Expert Perspectives: Evidence-Based Applications of Polynucleotides (PNs) in Aesthetic Medicine and Dermatology. Clinical, Cosmetic and Investigational Dermatology. 2026;19. doi:10.2147/CCID.S557226
- Arora G. Polynucleotides and polydeoxyribonucleotides in dermatology – A narrative review. Journal of Cutaneous and Aesthetic Surgery. 2026;19(1):17–28. doi:10.25259/JCAS_65_2025
- Retracted: PN-HPT® (Polynucleotides Highly Purified Technology) in facial middle third rejuvenation. Exploring the potential. Journal of Cosmetic Dermatology. 2022. doi:10.1111/jocd.14578
- VITARAN product information: 20 mg/mL polynucleotide; VITARAN I periocular (34G 4 mm microdroplet), VITARAN II face and body (25G cannula). Manufacturer brochure.
This article is for general information and is not personal medical advice. Always consult a doctor before deciding on any treatment.