Unraveling the Code for a Paradigm Shift in Cosmetic Actives
Dr. Paul Lawrence
Executive Director of Bioscience Research, Discovery, and Scientific Communications
Biocogent, LLC
Bio: Dr. Lawrence received his doctorate in molecular microbiology from Stony Brook University and before that obtained his Bachelor of Science degree in molecular biology from the University of New Mexico. During his career, he has conducted biological research in academia, industry, and for the United States government. He has executed anti-viral therapeutic and vaccine research projects at Brookhaven National Laboratory and the Plum Island Animal Disease Center. In industry, he has participated in contract biopharmaceutical projects for the former Collaborative Bioalliance as well as Dow Chemical. Dr. Lawrence was also the Director of DNA Production for the anti-counterfeiting biotechnology company, Applied DNA Sciences. Currently, he is the Executive Director of Bioscience Research, Discovery, and Scientific Communications for Biocogent, a developer and manufacturer of bio-active ingredients with cosmetic care applications. In his spare time, he is also an adjunct professor at three different colleges teaching microbiology to future nurses, doctors, and cosmetic care professionals. He has also been an instructor for several courses with the SCC’s continuing education program. He was also the Chair of the Committee on Scientific Affairs for the Society of Cosmetic Chemists (SCC). Over the course of his career, Dr. Lawrence has published more than 40 research manuscripts and review articles, more than 25 online science digests, and has authored a textbook chapter on the molecular pathogenesis of one of the world’s most infectious viruses.
Abstract: The cosmetic care industry frequently incorporates substances into finished products that are derived from three of the four major categories of biological molecules including carbohydrates, lipids, and peptides/proteins. But what about the fourth group – nucleic acids? Some might be surprised that there is a long history of using nucleic acids, both deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), as active components of cosmetic care products going all the way back to the 1970s. Now, scientists are employing small non-coding RNAs (ncRNAs) as powerful new active ingredients in skincare. These ncRNAs are embodied in two different forms: short interfering RNAs (siRNAs) and microRNAs (miRNAs). Both of these ncRNA molecules are the functional arms of an epigenetic mechanism known as “RNA interference” or “RNAi”, where they down-regulate the expression of certain genes in the human genome leading to diminished abundance of their encoded proteins. Recalling the “central dogma of biology”, genes found in the DNA of the genome are “transcribed” into a messenger RNA (mRNA) in the nuclei of our cells that then moves to the cytoplasm where it engages with the ribosomes (protein factories of the cell) to “translate” the mRNA into an amino acid sequence that will fold into a functional protein. miRNAs intercept the mRNA before it can interact with the ribosome, thus “interfering” with protein synthesis post-transcriptionally. Of the thousands of miRNA genes identified in humans, many of them exert influence over skin health.
For decades now, the cosmetic care industry has been amassing so-called “microRNA signatures” as molecular diagnostics for how the skin responds at the epigenetic level to environmental stimuli. Here, scientists have compared the expression levels of miRNAs in healthy skin to those of skin experiencing some form of disease of disorder. For example, a research group identified 4 miRNAs whose expression becomes dysregulated in individuals with a form of non-segmental vitiligo. They examined how an experimental topical therapy impacted the miRNA signature, which reverted back to homeostatic levels. This is just one example of many, but this diagnostic approach to understanding miRNAs and skin health is just one utility of this epigenetic mechanism. Others have taken a more “interventionist” strategy to benefiting skin health with RNA-based actives that can support healthy gene expression in the skin.
The small ncRNA constructs that have been employed for the interventionist application of RNAi for skin are frequently represented by what are known as “mimics” and “antagomiRs”. The former are replicas of naturally occurring miRNAs found in human skin that when delivered will bolster the endogenous levels of a particular miRNA thus further diminishing the cellular levels of its downstream protein targets. In contrast, the latter intercept specific miRNAs before they can impact the translation of a specific mRNA thus augmenting the synthesis of the encoded protein. Using mimics and antagomiRs, it is now possible to modulate the abundance of specific proteins like using a rheostat. Imagine the almost infinite applications of this approach! If you want to affect skin brightening, topically administer miRNAs that target tyrosinase, the key enzyme in the melanogenesis pathway. Alternately, if you want to strengthen the extracellular matrix, deploy an antagomiR targeting natural miRNAs that affect the genes for collagen, elastin, and fibrillin.
These concepts will be explored looking at proof-of-concept studies conducted at the lab bench that have evolved to in vivo clinical investigations. Moreover, new frontiers in the research of RNA actives will be touched upon for how this paradigm shift might continue into the future.