What polynucleotides actually are

1.1.1The chemistry, without the mystique

DNA is a polymer. It is built from nucleotides, and each nucleotide has three parts: a sugar, a phosphate group and one of four bases. Link enough of them together and you have a polynucleotide. That word is a description of structure, not of origin, purpose or effect. Starch is a polysaccharide; a polynucleotide is the equivalent term one level along in biochemistry.

What a clinic sells you as a polynucleotide injectable is that polymer, taken from a biological source, broken into fragments of a controlled size range, purified to remove as much of everything else as the manufacturing process can remove, sterilised, and suspended in a buffered saline solution. The finished product is a clear, somewhat viscous liquid. Its viscosity comes from the length of the chains and the concentration, in the same way that a long chain polymer thickens any solution it is dissolved in.

Two properties of the material matter for what follows. First, long chains of nucleotides in solution bind and hold water, and they form a loose physical network. Second, nucleotides are the raw material that cells use to build and repair their own nucleic acids, and cells possess salvage pathways that take up and reuse them. Almost every claim made for this treatment is built on one or both of those two facts.

1.1.2What it is not

This category attracts language borrowed from fields it does not belong to. It is worth stating the negatives plainly, because most of the confusion in a consultation comes from them.

• It is not a stem cell treatment. There are no cells in the syringe. There is no living material at all.
• It is not gene therapy and it does not alter your DNA. The fragments are short and are not delivered in any vector capable of entering a nucleus and integrating. The material is broken down in the tissue by ordinary enzymes.
• It is not a growth factor product. Growth factors are proteins. The purification process is specifically designed to remove protein.
• It is not a volumising filler. Volumising fillers work by occupying space and by drawing in water to occupy more space, and they are formulated to resist being broken down. Polynucleotide products are thinner, are placed differently, and are expected to disappear.
• It is not a licensed medicine in the ordinary sense. See the chapter on the regulatory category, because this is the single most misunderstood point in the whole subject.

1.1.3Why the fragments are short

Whole genomic DNA is enormous. It is far too long and too viscous to pass through a fine needle, and it is exactly the sort of material that provokes an immune response, because intact nucleic acid of the wrong kind is one of the things the innate immune system is built to detect. Manufacturing therefore involves deliberate fragmentation, usually by a combination of physical and enzymatic means, to produce chains in a defined size band.

Different manufacturers target different size bands, and the marketing around each product tends to insist that its particular band is the important one. Whether chain length within the ranges actually used makes a clinically meaningful difference to results in skin is not something the published record settles, and it is one of the more reliable indicators of promotional writing when a page asserts that it does.

1.1.4What else is in the syringe

The active material is a minority of the volume. The rest is a sterile buffered solution, typically a phosphate buffered saline, whose job is to hold the pH and osmolarity in a range the tissue tolerates. Some products include additional ingredients: a small quantity of hyaluronic acid, a local anaesthetic, or an antioxidant. Those additions change the product materially, and they also change how any claim about results should be read, because a study of a combination product cannot tell you what the polynucleotide component contributed on its own.

A practitioner should be able to tell you the full composition of the product they intend to use, from the instructions for use supplied by the manufacturer. If they cannot, that is a finding about the consultation rather than about the product.

1.1.5How it is expected to behave in tissue

Once injected into the dermis or just beneath it, the solution disperses. The chains hold water locally, which produces an immediate physical change: the tissue is briefly wetter and slightly more swollen. That accounts for some of what people notice in the first day or two, and it is a mechanical effect rather than a biological one.

Over the following days and weeks the material is degraded by nucleases, which are enzymes present throughout the body whose function is precisely to break down nucleic acid. The fragments become shorter, then become individual nucleotides, then are either taken up by cells through salvage pathways or excreted. Nothing is expected to remain in place in the long term. This is the reason the treatment is sold as a course with maintenance rather than as a single event, and it is also the reason there is no dissolving agent for it: there is nothing durable to dissolve.

1.1.6What this tells you before you have read anything else

Three practical consequences follow from the material description alone, and they are worth carrying into any consultation.

The first is that the effect, whatever it turns out to be, is temporary by design. Any claim of a permanent change from a substance that is engineered to be broken down within weeks needs a specific and separate explanation, and the only coherent one is that the material triggers a lasting change in the cells rather than persisting itself. That is a much bigger claim, and it needs much better evidence, than a claim about hydration.

The second is that a product that also contains hyaluronic acid, anaesthetic or an antioxidant is a different product, and results attributed to it cannot be transferred to a plain polynucleotide solution or the other way round.

The third is that because there is no reversal agent, the decision to have the treatment is less easily undone than the decision to have a hyaluronic acid filler. That does not make it more dangerous. It makes the pre treatment assessment more important, because if you dislike the result the available response is to wait.

1.1.7A note on the language used to sell it

Category marketing in this field leans on words with borrowed authority. Regenerative, biostimulatory, bio remodelling, cellular renewal and skin quality all sound like technical terms, and none of them has a fixed definition that a clinic is obliged to meet. They are not lies. They are unfalsifiable, which is worse for a reader trying to compare options, because an unfalsifiable claim cannot be wrong and therefore cannot be checked.

Wherever this reference encounters one of those words attached to a specific promise, it converts the promise into a claim that could in principle be tested and then reports what has actually been tested. That is what the evidence notes throughout this document are for.