It’s a new year, and I don’t know how your 2023 went, but we could really do with a good 2024 in the Flann household. Everyone from family, friends and patients had warned us that the first Christmas after a death in the family was the hardest so we prepared ourselves. I had a little wobbly on Christmas day thinking my dad was going to turn up at some point, he was just running a little late, but other than that, I think we held ourselves well.
It is therefore with a strong emphasis on positive mindset that we look forward to 2024 and it was interesting to read a paper on the development of gene editing creams and lipid nanoparticles to deliver targeted topical treatments.
[Guri-Lamce I, AlRokh Y, Kim Y et al. Topical gene editing therapeutics using lipid nanoparticles : “gene creams” for genetic skin diseases? British Journal of Dermatology, ljad528, https://doi.org/10.1093/bjd/ljad528]
What is gene editing?
This is where disease-causing changes in DNA are repaired either by exchanging the incorrect DNA sequences for correct ones or by providing the healthy correct DNA copy.
That sounds amazing! Why can’t we do this for everything?
Well, it is easier said than done. To correct the faulty DNA requires breaking the DNA which can lead to errors in the DNA and undesired insertions or deletions of genetic material. More often than not, only actively dividing cells can be targeted.
Also the way in which the gene editor is delivered is key as many are rapidly degraded when used on the body. This therefore requires that they are encapsulated in a delivery vehicle so that they can access the target organ or cell and perform their job.
The main delivery vehicles are basically, physical, viral or non-viral. Lipid nanoparticles (LNPs) are a non-viral delivery approach.
Why is it so complicated?
The skin acts as a barrier to prevent harmful organisms and chemicals from entering our bodies. The top layer of skin, called the stratum corneum is comprised of layers of keratin-filled skin cells that are embedded in a continuous matrix of fatty material. And the target for most active agents are the cells below this stratum corneum, in the epidermis and dermis.
How does a lipid nanoparticle work?
LNPs are a lipid-based delivery system which works to infiltrate the lipids in the stratum corneum. They can have their size adjusted, with the smallest LNPs penetrating into the deeper layers of skin. Peptides can be added which enable them to overcome barriers and they can be combined with other agents to improve potency.
LNPs have already been used to deliver gene editing treatments in the lab, are in trial stage in the mouse model to treat liver amyloidosis and a lung-targeting LNP has also been created.
As for the skin, they have also been used to accelerate diabetic wound healing, and have been used to deliver gene edited RNA to psoriatic skin.
How do we know it will work?
Vyjuvek ™ is a novel (2023), FDA approved topical gene therapy for a rare, genetic, blistering and skin fragility disorder called dystrophic epidermolysis bullosa (DEB). It delivers two normal copies of a certain collagen gene coding sequence to the skin cells using an engineered, non-replicating herpes simplex virus. It is mixed in a gel before being applied to the skin wounds of patients with DEB and causes closure and healing of most of these wounds within 3 months of treatment.
The future?
Well, it looks positive for this type of therapy. Though currently, there are no reports of gene editing being used in the skin, it feels like it won’t be long before we start hearing about it. And it will certainly transform the lives of those with genetic skin diseases for which we have had no treatments so far, and also possibly other skin diseases too.
Kind regards,
Sandy
Dr Sandy Flann, Consultant Dermatologist.
