Do You Know How Well Your Sunscreen Works?

Skin diseases caused by sun exposure include melanoma, basal cell carcinoma, squamous cell carcinoma, photoaging, as well as sunburn and many other conditions. According to the Skin Cancer Foundation, skin cancer is the most common type of cancer in the US. The vast majority of mutations found in melanoma, according to a 2009 study published in Nature [1], are caused by UV radiation.

Currently, commercial sunscreens are composed of physical sunblocks including zinc oxide and titanium dioxide, and chemical UV (ultraviolet lights) absorbers/filters such as octinoxate for UVB and benzophenone for UVA. The compositions of commercial sunscreen products are disclosed by the manufacturer and regulated by the health product regulatory authorities such the FDA in the US. The UV absorbers/filters are organic chemicals that absorb UV lights within a very limited range of wavelength. Consequently, a combination of different chemicals is needed to achieve “broad-spectrum” protection.

Currently the FDA required test of effectiveness of UV protection measures only UVB, which means there is no way of knowing how effective a sunscreen product is against cancer-causing UVA and damaging visible lights [2]. Even though the life style changes in recent time result in more damaging light exposure such as extended sun bathing on beach or tanning in beauty saloons, etc., only 3 new sunscreen active components (and none of new chemical class) have been introduced to the US market in more than 3 decades. There seems to be a gap between the need and the effort for developing substantially improved skin protection products.

1. Pleasance, E.D., R.K. Cheetham, P.J. Stephens, D.J. McBride, S.J. Humphray, C.D. Greenman, I. Varela, M.L. Lin, G.R. Ordonez, G.R. Bignell, K. Ye, J. Alipaz, M.J. Bauer, D. Beare, A. Butler, R.J. Carter, L. Chen, A.J. Cox, S. Edkins, P.I. Kokko-Gonzales, N.A. Gormley, R.J. Grocock, C.D. Haudenschild, M.M. Hims, T. James, M. Jia, Z. Kingsbury, C. Leroy, J. Marshall, A. Menzies, L.J. Mudie, Z. Ning, T. Royce, O.B. Schulz-Trieglaff, A. Spiridou, L.A. Stebbings, L. Szajkowski, J. Teague, D. Williamson, L. Chin, M.T. Ross, P.J. Campbell, D.R. Bentley, P.A. Futreal, and M.R. Stratton, A comprehensive catalogue of somatic mutations from a human cancer genome. Nature. 463(7278): p. 191-6.
2. Botta, C., C. Di Giorgio, A.S. Sabatier, and M. De Meo, Genotoxicity of visible light (400-800 nm) and photoprotection assessment of ectoin, L-ergothioneine and mannitol and four sunscreens. J Photochem Photobiol B, 2008. 91(1): p. 24-34.

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Tags: fluorescence, light exposure, melanoma, skin cancer, skin care, spectra, spectrum, sunburn, sunscreen, UVA, UVB, visible light

Delivery of RNAi or Cre by Ultrasound-Guided Injection of High Titer Lentiviral Vectors

By Jiwu Wang

According to the Skin Cancer Foundation, skin cancer is the most common type of cancer in the US. Although the skin might seem to be an easy target for gene therapy or RNAi mediated functional corrections, the outer keratinized epithelial cells forms a formidable barrier to delivery of genetic material. The epidermis undergoes rapid turnover, a fact that further complicates gene therapy because gene transfer to skin stem cells would be required for sustained effects.

Before skin gene therapy can be discussed with any practical meaning, a physiologically relevant in vivo model for studying gene function in the context of tumorigenesis and epithelial biology must be established. Studies of gene functions in skin homeostasis in mouse models were mostly performed by labor-intensive knockout methods. Recently, at least two publications have shown that by using ultrasound-guided injection of lentiviruses into amniotic fluids, transgene or shRNA can be efficiently and specifically delivered to epidermis, including skin stem cells, creating a very attractive model for functional studies and therapeutic tests.

Localized injection of high titer lentiviral vectors has been widely used for studying genes in brain development and a few other areas. Instead of injection into animal tissues, Endo et al. injected tiny volume (nl) of high titer lentivirus (10e10 TU/ml) into amniotic cavities within a defined window of embryogenesis [1]. By following fluorescent protein markers (CFP, GFP, YFP, RFP), both Endo et al. and researchers from Elaine Fuchs group demonstrated high efficiency and specificity of delivery to epithelial cells, commonly resulting in multiple genomic insertions of the viral genome.

RNAi against alfa1-catenin was used by Beronja and colleagues as an example to show that loss-of-function analysis can be done rather easily using shRNA/FP bearing lentivirus [2]. nlCre was also delivered to embryos with loxP-flanked transgenes vs wildtype for conditional knockout studies. These new findings should open doors to various experiments and therapies concerning the health of the skin.

1. Endo, M., P.W. Zoltick, W.H. Peranteau, A. Radu, N. Muvarak, M. Ito, Z. Yang, G. Cotsarelis, and A.W. Flake, Efficient in vivo targeting of epidermal stem cells by early gestational intraamniotic injection of lentiviral vector driven by the keratin 5 promoter. Mol Ther, 2008. 16(1): p. 131-7.
2. Beronja, S., G. Livshits, S. Williams, and E. Fuchs, Rapid functional dissection of genetic networks via tissue-specific transduction and RNAi in mouse embryos. Nat Med. 16(7): p. 821-7.

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Tags: cre, Fluorescent proteins, in vivo injection, lentiviral vector, lentivirus, loxP, nlCre, RNAi, shRNA, skin cancer, skin care, skin therapy, sunscreen, transgene