ENHANCEMENT OF ULTRAVIOLET‐DNA REPAIR IN den V GENE TRANSFECTANTS and T4 ENDONUCLEASE V‐LIPOSOME RECIPIENTS

Kibitel, Jeannie; Yee, Vivian; Yarosh, Daniel B.

doi:10.1111/j.1751-1097.1991.tb02086.x

Cited by 31 publications

(6 citation statements)

References 25 publications

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“…It is hypothesized that exogenous delivery of BER-initiating repair enzymes to UV-exposed skin cells may promote rapid, accurate repair of CPDs, providing protection against skin cancer. Indeed, the bacteriophage T4 pyrimidine dimer-specific DNA glycosylase (T4-pdg), also called T4 endonuclease V, enhances repair of CPDs and reduces the frequency of UV-induced mutations in cultured mammalian cells when introduced by DNA transfection or by direct protein delivery via encapsulation into a liposomal delivery vehicle (Cafardi and Elmets, 2008; Francis et al , 2000; Kibitel et al , 1991; Kusewitt et al , 1994; Kusewitt et al , 1998; Yarosh et al , 1992). …”

Section: Introductionmentioning

confidence: 99%

TAT-Mediated Delivery of a DNA Repair Enzyme to Skin Cells Rapidly Initiates Repair of UV-Induced DNA Damage

Johnson

Lowell

Ryabinina

et al. 2011

Journal of Investigative Dermatology

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Ultraviolet (UV) light causes DNA damage in skin cells, leading to more than one million cases of non-melanoma skin cancer diagnosed annually in the United States. Although human cells possess a mechanism (Nucleotide Excision Repair, NER) to repair UV-induced DNA damage, mutagenesis still occurs when DNA is replicated prior to repair of these photoproducts. While human cells have all the enzymes necessary to complete an alternate repair pathway, Base Excision Repair (BER), they lack a DNA glycosylase that can initiate BER of dipyrimidine photoproducts. Certain prokaryotes and viruses produce pyrimidine dimer-specific DNA glycosylases (pdgs) that initiate BER of cyclobutane pyrimidine dimers (CPDs), the predominant UV-induced lesions. Such a pdg was identified in the Chlorella virus PBCV-1 and termed Cv-pdg. The Cv-pdg protein was engineered to contain a nuclear localization sequence (NLS) and a membrane permeabilization peptide (TAT). Here, we demonstrate that the Cv-pdg-NLS-TAT protein was delivered to repair-proficient keratinocytes and fibroblasts, and to a human skin model, where it rapidly initiated removal of CPDs. These data suggest a potential strategy for prevention of human skin cancer.

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Section: Introductionmentioning

confidence: 99%

TAT-Mediated Delivery of a DNA Repair Enzyme to Skin Cells Rapidly Initiates Repair of UV-Induced DNA Damage

Johnson

Lowell

Ryabinina

et al. 2011

Journal of Investigative Dermatology

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“…By cleaving DNA at the site of UV-induced lesions, the enzyme reverses the DNA repair defect of XP cells (Yarosh, 2002). Further work by the same group also showed that these T4N5 liposomes in a 1% hydrogel lotion when applied in cultured human fibroblasts, mouse dorsal back or cultured human breast skin is capable of delivering the enzyme into cells in less than one hour, being almost entirely restricted to the epidermis (Ceccoli et al, 1989;Kibitel et al, 1991). An inverse correlation was later shown between the T4N5 dose and the level of CPDs that remained in the epidermis.…”

Section: Topical Use Of T4 Endonucleasementioning

confidence: 97%

Recombinant Viral Vectors for Investigating DNA Damage Responses and Gene Therapy of Xeroderma Pigmentosum

Quayle¹,

Menck²,

Lima-Bessa³

2011

DNA Repair and Human Health

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“…Removal of CPD was measured in SV-40 transformed normal and XP-A fibroblasts irradiated with 25 J/m 2 of UV-C. Treatment with between 0.04 and 0.2 mg/ml of T4N5 liposomes increased the removal of CPDs at 6 h in either of two normal fibroblast strains (53). No repair occurred in the UV-irradiated XP-A fibroblasts during the 6-h period, but cells treated with 0.04 and 0.2 mg/ml of T4N5 liposomes showed repair of between 40 and 47% of the CPDs.…”

Section: Repair Of Dna Damagementioning

confidence: 99%

Liposomes in investigative dermatology

Yarosh

2001

Photoderm Photoimm Photomed

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Liposomes are microscopic spheres, usually composed of amphiphilic phospholipids. They may be useful without skin penetration if they simply protect or sequester compounds that would otherwise be unstable in the formulation. Liposomes that remain on the skin surface are useful as light-absorbers, agents to deliver color or sunscreens, or as depots for timed-release. Liposomes that penetrate the stratum corneum have the potential to interact with living tissue. Topically applied liposomes can either mix with the stratum corneum lipid matrix or penetrate the stratum corneum by exploiting the lipid-water interface of the intercellular matrix. There are at least four major routes of entry into the skin: pores, hair follicles, columnular spaces and the lipid:water matrix between squames. A major force driving liposome penetration is the water gradient, and flexible liposomes are best able to exploit these delivery opportunities. Some liposomes release their contents extracellularly. Topical application of photosensitizers may be enhanced by encapsulation in liposomes. Higher and longer-lasting drug concentrations may be produced in localized areas of skin, particularly at disease sites where the stratum corneum and the skin barrier function are disrupted. The liposome membrane should be designed to capture lipophilic drugs in the membrane or hydrophilic drugs in the interior. Other types of liposomes can be L iposomes are microscopic vesicles, usually formed from phospholipids. The useful phospholipids are amphipathic, in that they have both lipophilic and hydrophilic moieties. Under the right conditions these molecules will stack on solid supports to form membranes, with the hydrophilic head groups arranged on one side of the array, and the hydrophilic tail groups on the other. In aqueous solution, these arrays spontaneously form bilayers membranes in the shape of a sphere, which are called liposomes (1). Here the hydrophilic head groups point out toward water, and the lipophilic tails point to 203 engineered to be taken up by cells. Once inside cells, the lysosomal sac and clatherin-coated pit are the dead-end destinations for liposomes unless an escape path has been engineered into the liposome. A novel method has been developed to allow delivery into cells of the skin, by escape from the lysosomal sac. These liposomes have been used to topical deliver active DNA repair enzymes from liposomes into epidermal cells and to enhance DNA repair of UV-irradiated skin. From these studies a tremendous amount has been learned about the relationship of DNA damage and skin cancer. Both mutations and immunosuppression appear to be essential to skin cancer and both are induced by DNA damage. DNA damage produces immediate effects by inducing the expression of cytokines, which means that DNA damage can induce signaling in neighboring, undamaged cells. The repair of only a fraction of the DNA damage has a disproportionate effect on the biological responses, clearly demonstrating that not all DNA damage is equivalent. This technolo...

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ENHANCEMENT OF ULTRAVIOLET‐DNA REPAIR IN den V GENE TRANSFECTANTS and T4 ENDONUCLEASE V‐LIPOSOME RECIPIENTS

Cited by 31 publications

References 25 publications

TAT-Mediated Delivery of a DNA Repair Enzyme to Skin Cells Rapidly Initiates Repair of UV-Induced DNA Damage

TAT-Mediated Delivery of a DNA Repair Enzyme to Skin Cells Rapidly Initiates Repair of UV-Induced DNA Damage

Recombinant Viral Vectors for Investigating DNA Damage Responses and Gene Therapy of Xeroderma Pigmentosum

Liposomes in investigative dermatology

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