Indian Journal of Dermatology
  Publication of IADVL, WB
  Official organ of AADV
Indexed with Science Citation Index (E) , Web of Science and PubMed
Users online: 2655  
Home About  Editorial Board  Current Issue Archives Online Early Coming Soon Guidelines Subscriptions  e-Alerts    Login  
    Small font sizeDefault font sizeIncrease font size Print this page Email this page

Year : 2006  |  Volume : 51  |  Issue : 3  |  Page : 211-216
Gene therapy in dermatology

Institute of Allergic and Immunologic Skin Diseases, Kolkata, India

Correspondence Address:
Nilendu Sarma
P. N. Colony, Sapuipara, Bally, Howrah - 711 227
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.27992

Rights and Permissions

How to cite this article:
Sarma N. Gene therapy in dermatology. Indian J Dermatol 2006;51:211-6

How to cite this URL:
Sarma N. Gene therapy in dermatology. Indian J Dermatol [serial online] 2006 [cited 2022 Jan 27];51:211-6. Available from:

   Introduction Top

Introduction of a normal gene into cells or tissues which have defective genes for the treatment of genetic disease is called gene therapy. However gene therapy for the non-genetic diseases has also been attempted.

Non-therapeutic use include prevention or understanding the pathogenesis of a disease. Although delivery of the genes into the cells requires similar techniques, they are by definition not gene therapy.

The basic technique of gene therapy

Introduction of a correct gene replacing a defective one will re-establish the normal functioning of the body. A functional gene can be introduced in the cell by different methods. Most common method that is used currently is to insert the gene into a non-specific location of genome and it replaces a non-functional gene.

However the better approaches are to replace the defective gene with a correct gene through homologous recombination, or use of selective reverse mutation to normalise the defect and synthesize a normal mRNA.

Different techniques of genetic corrections are gene restoration, gene augmentation, gene correction and gene inhibition.[1] In erythropoietin-responsive anaemia, gene augmentation is required.[2]

In case of small point mutations leading to development of a defective gene, gene correction is needed using small DNA/RNA chimeric molecules.

Antisense nucleic acids[3] and ribozymes[4] are two methods of gene inhibition.

In-vivo vs ex-vivo technique of gene therapy

In vivo
technique means the genes are delivered directly in the skin of the host by different methods like injection, electroporation, gene gun, topical application to normal and wounded skin surfaces and bioplastic particle insertion etc.[5] In contrast, in ex-vivo technique, the gene is transferred into the cells out side the body into the skin cells taken out. It produces a much higher level of transduction, precisely introduce the gene in correct types of target cells (keratinocytes, or fibroblasts) and there is less chance of immune reaction.

Animal model

Mice are used in almost all studies of in vivo keratinocyte gene therapy. However recently this has been questioned due to morphological differences between the mice and human skin.[6]


The molecule that carries the therapeutic gene to the target gene or cell is called vector. Vectors are of basically two types, viral and non-viral. Success of a gene therapy depends heavily on proper selection of vector.


By definition, the retrovirus has RNA as the sole genetic material. This is converted by 'reverse transcriptase' to DNA and then it is attached with host DNA by another enzyme called 'integrase'. Retroviruses attach themselves to a arbitrary location in the host's DNA. This can have some serious implication. It can break some important regulatory gene or more seriously can disrupt some growth regulator leding to uncontrolled growth and even development of cancer.[7] To prevent this, specialised techniques have been developped like use of 'zinc finger nucleases'[8] or incorporation of specific sequences such as the 'beta-globin locus control region'.


Unlike retrovirus, genetic mateials of adenovirus, which is a double-stranded DNA, cannot attach themselves with the host DNA and float free in the the nucleus of the host cell. So it is not transmitted to the descendants of the host cell. So repeated treatment is required to treat the newly generated cells.

   Adeno-associated viruses (AAV) Top

They are non-pathogenic parvovirus having a single stranded DNA. They can infect quiescent cells like neuron. It makes them most suitable to use for treatment of brain disease. They are also very suitable for treatment of muscle and eye disease. However they stimulate strong immune reaction.[9]

Non-viral methods

Non viral vectors are safer than viral one but have poor transduction capacity with an average rate of only 30%.[10] To improve this 'electroporation' or 'gene gun' techniques have been developed. Elctroporation based newer transfection method has increased the transduction rate to a somewhat higher value of 56%.[11] Further advancement to improve this transient gene expression has developped P-1 based artificial chromosome (PAC construct) and its capacity has been tested to produce stable type VII collagen gene expression in DEB.[12]

Naked DNA

Naked DNA is histone-free DNA that gives a new phenotype to the recipient cell during 'transformation' process. Naked DNA plasmid or even naked PCR product has been used in gene therapy. Gene therapy using naked DNA is simple, safe and an efficient method. The plasmid DNA is directly intradermally injected.[13] The gene is incorporated mainly to the keratinocytes and very little to the fibroblast[13] and selectively expressed at upper and middle layer of epidermis.[13],[14] However semiquantitative analysis of the result of transgene expression of IL-6 gene showed that intially it is incorporated into the basal keratinocytes but the expression was lost early to remain in the spinous layer for a prolonged period.[15]

Recently Hengge et al[16] suggested a specific receptor for the plasmid DNA on the surface of keratinocytes. In another intersting development, a small transporter protein called 'high mobility group 1' has been detected in the nucleus of keratinocytes that assists in transport of DNA from cytosol to nucleus.[17]

   Hybrid Methods Top

Here viral vectors are combined with nonviral vectors, e.g., virosomes.

Hurdles of gene therapy:

l Transient gene expression

l Immune reaction

l Problems with viral vectors

l Multigene disorders

l Chance of inducing a tumor

Reasons of transient gene expression:

1. Poor selection of holoclone keratinocytes.

2. Retroviral vectors produce longer gene expression than non viral vectors or adenovirus.

3. Transient gene expression may be down-regulated due to methylation induced silencing of promoter element by the host.[18],[19]

4. Episomal expression vector is lost during progeny segregation.[20]

Strategies for sustained gene expression

1. Viral vectors can help prolonged gene expression especially lentiviruses directed to dermal fibroblasts and endothelial cells[2] and AAV directed to the panniculus carnosus.[21] Unfortunately the panniculus carnosus is not present in human beings.

2. Pseudotyped retrovirals when placed invivo under wound eschar produced via dermabrasion can generate persistent gene expression.[22]

   Immune Reaction Top

Immunology has been in the centre of attention of recent research work.[23] Introduced gene as well as the viral vectors are protein structure (especially the protein envelop). So it faces all the consequence of any foreign proteins inside the body. Both CD4 and CD8 cells participate in the immune response.[24] More importantly, immune reaction elicited by memory cells in subsequent therapies makes the situation worse. Viral vectors have been found to stimulate dendritic cells (DC) through type 1 interferons and phosphatidylinositol 3-kinase pathway.[25]

Ways to prevent immune reaction

1. Generation of tolerogenic DC with the help of IL10 treatment, ligation of CD45RO/RB and NVP347 treatment.[23],[26]

2. Role of 'Tregs' (transfer of regulatory T cells): Depletion of Tregs can lead to increased tumor growth. Tregs has the potential to be used as treatment option for transplant rejection and autoimmunity and also in preventing immunoreactivity in gene therapy.[23]

3. Blockade of CD28 and CD40 pathway,[27] antibody to CD45RB[28] and other strategies.[29]

   Gene therapy in skin the advantages Top

Keratinocytes are the target cells of choice in gene therapy for skin diseases and many systemic diseases. The reasons are :

1. Keratinocytes are easily accessible.[30]

2. Rich vascularization in dermis.

3. The genetically modified regions can be easily monitored.

4. Surgical removal of aberrant tissue if required.[31]

5. Skin is a versatile bioreactor: It can synthesize and secrete the proteins into the systemic circulation. It has been found that when transduced with the transgene of growth hormone, transferrin, erythropoietin, apolipoprotein E and factor IX, it delivered the active factors into the circulation.[2],[32],[33],[34],[35] It has been seen that not only the transgene products are secreted in the circulation, the physiological effects of these transgenes are also observed.[36] Their ability to secret the gene products in the circulation has been further enhanced with recent advancement in approaches like modified progesterone receptor driven transcription.[37] A study has shown that nearly 70 proteins were secreted into the medium by the keratinocytes.[38] Studies have shown that even cytokines like IL4, IL6, IL10, monocyte chemotactic and activating factor (MCAF), GM-CSF, IFN gamma etc., can be synthesized in this way in tranduced keratinocytes followed by systemic secretion.[39] It has been found that a single direct injection of erythropoietin gene with lentiviral vector into human skin xenografts on immune deficient mice produced persistent elevation of hematocrit for nearly 1 year.[2]

Other than keratinocytes, fibroblast, melanocytes, macrophage, endothelial cells all have been used as target cells in skin gene therapy.

Melanocytes are difficult to study because of scarcity of avilable vectors for efficient transduction in the melanocytes. Adenovirus can transduce in the melanocytes but are very short lasting. Lentivirus has been found to have the most efficient transduction capacity (95-100%) and persist for several weeks in 95-100% of the infected melanocytes.[40]

Target sub-population of cells: Role of stem cell

Studies proved that gene therapy targeting stem cells offer longer duration of gene expression than other cells because, with cell divisions, such stem cells are not depleted. Transgene expression has been observed for the entire lifespan of those stem cells (more than 150 cell generations).[41]

Stem cells in keratinocyte population is called holoclone keratinocytes. These are the best target cells for gene therapy. Intermediate meroclones can also be targeted as the T cells in treatment of blood disorders.[42]

   Gene therapy in dermatology Top

Genetic diseases are the targets for gene therapy, especially the monogenetic diseases. Treatment of recessive patterns is easier as correction of only one defective gene can correct the defect in comparison to the dominant patterns where single gene correction cannot correct the defect, except in happloinsufficiency. Other than genetic diseases, important advancement has been made in the treatment skin cancer, skin wounds and intractable inflammatory skin disease.[18],[31],[43]

   Inherited Skin Disorders Top

Epidermolysis bullosa (EB)

Till date, defect in ten etiological genes have been identified. A good number of EB cases develop aggressive squamous cell carcinoma. So the benefit of gene therapy outweighs the risk associated with it, especially considering the fact of unavailability of any acceptable therapy.

EB simplex (EBS)

Mutation affects the KRT5 and KRT14 keratin genes. Oligonucleotide mediated gene correction techniques have been used. In addition, related techniques like antisense technology and RNA interference have also been used.


1. It is inherited dominantly. So gene therapy is difficult.

2. Mutant allele acts a poison to the cell requiring silencing of that in addition to introduction of a correct gene. Specific slilencing is a potentially promising approach[44] but silencing of the mutant allele without attacking the neighbouring normal one, is extremely difficult. Inspite of these difficulties, success of some studies offers hope in the treatment of EBS.[45]

Junctional EB (JEB)

Traditionally it has been divided into two types - Herlitz (H-JEB) and non-Herlitz (NH-JEB) types. LAMA3, LAMB3 and LAMC2 genes encode three chains of laminin 5- a3, b3 and c2 respectively. LAMB3 gene is the most frequently affected gene by mutations in H-JEB.

Retroviral vector has been the most effetive vector as found in the work by Dellambra et al and Robbins et al using LAMB3 cDNA gene.[46]

Ortiz-Urda et al used a non-viral vector called FC31 integrase, a transporon (sleeping beauty) using 'cut and paste' techniques.[47]

Both BP180-deficient and laminin - 5-deficient junctional EB have been corrected via ex-vivo technique using human skin graft/immune deficient mouse xenograft model.[48],[49]

Dystrophic EB

Large sizes of the defective genes are major hurdles in the therapy of DEB. Sizes of type VII collagen and plectin cDNA are 9 and 14kb respectively, making them difficult to transport via available vectors. However Sawamura et al recently was able to introduce a 9kb gene via a plasmid DNA.[15]

In-vivo approaches have been made with intradermal injection of:

1. Gene-corrected RDEB fibroblast.

2. Lentiviral vectors carrying the ColVII gene.

3. Recombinant human type collagen.

In an intersting article, Maki Goto et al showed that fibroblast is a better target cell than keratinocyte as the former produced higher amount of collagen VII.[50]

   Xeroderma pigmentosum Top

This is a genetic disorder transmitted via both dominant and recessive modes. The patients suffer from inefficient nucleotide repair (NER) of ultraviolet ray (UV) induced mutations in DNA. NER is the most efficient DNA repair system, so defect in this culminates in serious mutagenesis and finally skin cancers[51] in most, even before 30 years of age.

Seven genes have been identified from XPA to XPG, defect in which result in NER defect in XP.[52]

Considering the advantage of adenoviruses over retroviruses like capacity to transduce into neurone cells and selective location for transfection, they are used more frequently. Studies by other authors found that lentivirus could be an attractive alternative vector due to its stability and highly efficient transduction into the postmeiotic neurones.[53],[54] Study on viral-mediated expression of XP in fibroblasts has been found to correct the DNA repair deficiency of primary skin fibroblasts isolated from these patients.[55]

However to avoid the risk of insertional mutagenesis, use of plasmid DNA vector should be considered.

   Ichthyosis Top

Lamellar Ichthyosis

Lamellar ichthyosis (LI) is a recessive, X-linked disorder due to a defect in enzyme transglutaminase (Tgase1) that is involved in the formation of the cornified epithelium (CE)

Choate et al have shown that in-vitro retroviral transduction of primary keratinocytes taken from affected LI patients could restore defective involucrin cross-linking[56] and filaggrin[57] and restored the function of the cutaneous barrier in immunodeficient mice.

X-linked Ichthyosis

X-linked ichthyosis is caused by a deficiency in steroid sulphatase (STS). There is accumulation of cholestrol sulphate called 'arylsulphatase C'. Clinically it resuls in abnormal scaling skin.

In 90% of cases, the gene is completely deleted and in the rest, it is partially deleted. Transfection in vitro with the gene encoding STS leads to increased cell maturation and partial correction of the phenotype. The major challenge is early loss of transgene expression which is more common with nonviral naked DNA or plasmid mediated methods than with retroviral vector driven transduction.

Other types of ichthyosis

There is sufficient hope for correction of congenital bullous ichthyosiform erythroderma of the Brocq and Siemens types, caused by mutations in keratins 1, 2e or 10. Antisense probe targeted against a mutated allele to knock out the expression of the dominant negative protein can correct the defect. But practically it is yet to be achieved because of two reasons. A good antisense is hard to find and more importantly the location of the mutation varies widely in families.


Porthyria is a disorder of haematopoitic system. However skin symptoms are marked in most of them. Erythropoietic protoporphyria (EPP) is caused by a ferrochelatase deficiency and is characterized by severe skin photosensitivity and accumulation of protoporphyrin in bone marrow, RBC and some other organs. Gene therapy for this disease has been tried with a self-inactivating lentiviral vector containing human ferrochelatase cDNA driven by the human ankyrin-1/b-globin HS-40 chimeric erythroid promoter/enhancer in mice. Specific ferrochelatase gene was efficiently transferred in bone marrow erythroid lineage that corrected almost all clinical and biological alterations including skin photosensitivity


There are certain differences of a wound from genodermatoses so also in the gene therapy:

1. The epidermal barrier is lacking so gene transfer is easier.

2. Area to be treated is limited.

3. Requirement for gene expression is for only limited period till the ulcer is healed.

So the methods, which classically produce short lasting gene expreesion like nonintegrative viral vectors, can be used.

Gene-gun delivery, direct application of naked DNA, electroporative transfer, intraulcer injection, microvascular transfection or wound bed implantation are other techniques used.

Gene therapy offers valuable treatment options for non-genetic diseases such as severe burns and refractory skin wounds of decubital, vascular or diabetic origin. It aims at enhancing wound-healing rate, inhibiting postulcer complications, e.g., scarring and keloid formation, as well as increasing the tensile strength of newly formed skin.

In-vivo approach has shown that expression of exogenous epidermal growth factor in the skin increases wound healing by 20%.[58]

Collagen-embedded PDGF-B DNA plasmid[59] [41] or a viral vector carrying the PDGF-B gene[60] [42] has been introduced in rabbit to improve healing. PDGF-A, KGF, insulin like growth factor (IGF-1) genes have been transduced for increasing the granulation tissue synthesis in other studies. Exogenous expression of IGF enhanced keratin growth in vitro and stimulated proliferation in vivo , without altering epidermal differentiation

Pre-clinical studies have been undertaken in vivo with VEGF, iNOS and EGR 1 (early growth response factor 1) genes for increasing the vascularization to a similar degree. EGF and GH genes were used for repithelialization.[1]

Of particular interest is use of TGF-b and FGF genes in preventing scarring and fibrosis during wound healing. Antisense oligonucleotides have been used to enhance functioning of collagen genes.

Squamous cell carcinoma (SCC)

Successful treatment of SCC in mice by transfection with herpes simplex thymidine kinase (HSVTK) 'suicide' gene followed by treatment with gancyclovir by a adenovirus marked an important progress towards cancer gene therapy.[61]


Quite a few studies have been undertaken for treatment of melanoma with gene therapy, like genetically modified fibroblasts, tumour cells, direct injection of vaccinia and adenoviruses encoding cytokines.

   References Top

1.Khavari PA, Rollman O, Vahlquist A. Cutaneous gene transfer for skin and systemic diseases. J Intern Med 2002;252:1-10.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Baek SC, Lin Q, Robbins PB, Fan H, Khavari PA. Sustainable systemic delivery via a single injection of lentivirus into human skin tissue. Hum Gene Ther 2001;12:1551-8.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Wraight CJ, White PJ. Antisense oligonucleotides in cutaneous therapy. Pharmacol Ther 2001;90:89-104.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Lewin AS, Hauswirth WW. Ribozyme gene therapy: Applications for molecular medicine. Trends Mol Med 2001;7:221-8.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Robbins PB, Khavari PA. Strategies for cutaneous gene therapy. Curr Probl Dermatol 2000;12:198-203.  Back to cited text no. 5      
6.Hengge UR, Walker PS, Vogel JC. Expression of naked DNA in human, pig, and mouse skin. J Clin Invest 1996;97:2911-6.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]  
7.Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, et al . LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003;302:415-9.   Back to cited text no. 7      
8. Durai S, Mani M, Kandavelou K, Wu J, Porteus MH, Chandrasegaran S. Zinc finger nucleases: Custom-designed molecular scissors for genome engineering of plant and mammalian cells. Nucl Acids Res 2005;33:5978-90.  Back to cited text no. 8      
9.YangY, Nunes FA, Berencsi K, Furth EE, Gonczol E, Wilson JM. Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proc Natl Acad Sci USA 1994;91:4407-11.  Back to cited text no. 9      
10.Chen M, Li W, Fan J, Kasahara N, Woodley D. An efficient gene transduction systemfor studying gene function in primary human dermal fibroblast and epidermal keratinocytes. Clin Exp Dermatol 2003;28:193-9.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Distler JH, Jungel A, Kurowska-Stolarska M, Michel BA, Gay RE, Gay S, et al . Nucleofection: A new, highly efficient transfection method for primary human keratinocytes. Exp Dermatol 2005;14:315-20.  Back to cited text no. 11      
12.Mecklenbeck S, Compton SH, Mejia JE, Cervini R, Hovnanian A, Bruckner-Tuderman L, et al . A microinjected COL7A1-PAC vector restors synthesis of intact procollagen VII in a dystrohic epidermolysis bullosa keratinocytes cell line. Hum Gene Ther 2002:13:1655-62.  Back to cited text no. 12      
13.Hengge UR, Chan EF, Foster RA, Walder PS, Vogel JC. Cytokine gene expression in epidermis with biological effects following injection of naked DNA. Nat Gen 1995;10:161-6.  Back to cited text no. 13      
14.Sawamura D, Meng X, Ina S, Ishikawa H, Tamai K, Nomura K, et al . In vivo transfer of a foreign gene to keratinocytes using the hemagglutinating virus of Japan-liposome method. J Invest Dermatol 1997;108:195-9.   Back to cited text no. 14      
15.Sawamura D, Yasukawa K, Kodama K, Yokota K, Sato-Matsumura KC, Toshihiro T, et al . The majority of keratinocytes incorporate intradermally injected plasmid DNA Regardless of size but only a small proportion of cells can express the gene product. J Invest Dermatol 2002;118:967-71.  Back to cited text no. 15      
16.Hengge UR, Tachakarjan E, Mirmohammdsadegh GM, Meyer HE. Uptake of DNA by keratinocytes. In : Hengge UR, Volc-Platzer B, editors. The Skin and Gene Therapy, 1st ed. Springer: Berlin; 2001. p. 81-94.  Back to cited text no. 16      
17.Ina S, Sawamura D, Meng X, Tamai K, Hanada K, Hashimoto I. In vivo gene transfer method in keratinocyte gene therapy. Intradermal injection of DNA complexed with high morbility-1 protein in rats. Acta Derm Venereol 2000;80:10-3.   Back to cited text no. 17  [PUBMED]    
18.Palmer TD, Rosman GJ, Osborne WR, Miller AD. Genetically modified skin fibroblasts persist long after transplantation but gradually inactivate introduced genes. Proc Natl Acad Sci USA 1991;88:1330-4.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]  
19.Khavari PA. Gene therapy for genetic skin disease. J Invest Dermatol 1998;110:462-7.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]  
20.Trainer AM, Alexander MY. Gene delivery to the epidermis. Hum Mol Gen 1997;6:1761-7.  Back to cited text no. 20      
21.Donahue BA, McArthur JG, Spratt SK, Bohl D, Lagarde C, Sanchez L, et al . Selective uptake and sustained expression of AAV vectors following subcutaneous delivery. J Gene Med 1999;1:31-42.  Back to cited text no. 21      
22.Ghazizadeh S, Harrington R, Taichman L. In vivo transduction of mouse epidermis with recombinant retroviral vectors: Implications for cutaneous gene therapy. Gene Ther 1999;6:1267-75.  Back to cited text no. 22  [PUBMED]  [FULLTEXT]  
23.Tan PH. 9th American Society of Gene Therapy Annual Meeting. Expert Opin Biol Ther 2006;6:839-42.  Back to cited text no. 23  [PUBMED]  [FULLTEXT]  
24.Ghazizadeh S, Kalish RS, Taichman LB. Immune mediated loss of transgene expression in skin: Implication for cutaneous gene therapy. Mol Ther 2003;7:296-303.  Back to cited text no. 24      
25.Tan PH, Butelspacher SC, Xue SA, Wang YH, Mitchell P, McAlister JC, et al . Modulation of human dendritic cell function following transduction with viral vectors: Implication for gene therapy. Blood 2005;105:3824-32.  Back to cited text no. 25      
26.Tan PH, Yates JB, Xue SA, Chan C, Jordan WJ, Harper JE, et al . Creation of tolerogenic human dendritic cells via intracellular CTLA4: A novel strategy with potential in clinical immunosuppression. Blood 2005;106:2936-43.  Back to cited text no. 26      
27.Larsen CP, Elwood ET, Alexander DZ, Ritchie SC, Hendrix R, Tucker-Burden C, et al . Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 1996;381:434-8.  Back to cited text no. 27      
28.Lazarovits AI, Poppema S, Zhang Z, Khandaker M, Le Feuvre CE, Singhal SK, et al . Prevention and reversal of renal allograft rejection by antibody against CD45RB. Nature 1996;380:717-20.  Back to cited text no. 28      
29.Zhao Y, Swenson K, Sergio JJ, Arn JS, Sachs DH, Sykes M. Skin graft tolerance across a discordant xenogeneic barrier. Nat Med 1996;2:1211-6.  Back to cited text no. 29  [PUBMED]    
30.Hengge UR, Volc-Platzer B. The skin and the gene therapy. 1st ed. Springer: Hydelburg, Germany; 2001.  Back to cited text no. 30      
31.Greenhalgh DA, Rothnagel JA, Roop DR. Epidermis: An attractive target for gene therapy. J Invest Dermatol 1994;103:63S-9S.   Back to cited text no. 31  [PUBMED]    
32.Morgan JR, Barrandon Y, Green H, Mulligan RC. Expression of an exogenous growth hormone gene by transplantable human epidermal cells. Science 1987;237:1476-9.   Back to cited text no. 32  [PUBMED]  [FULLTEXT]  
33.Petersen MJ, Kaplan J, Jorgensen CM, Schmidt LA, Li L, Morgan JR, et al . Sustained production of human transferrin by transduced fibroblasts implanted into athymic mice: A model for somatic gene therapy. J Invest Dermatol 1995;104:171-6.  Back to cited text no. 33      
34.Fenjves ES, Gordon DA, Pershing LK, Williams DL, Taichman LB. Systemic distribution of apolipoprotein E secreted by grafts of epidermal keratinocytes: Implications for epidermal function and gene therapy. Proc Natl Acad Sci USA 1989;86:8803-7.   Back to cited text no. 34  [PUBMED]  [FULLTEXT]  
35.Gerrard AJ, Hudson DL, Brownlee GG, Watt FM. Towards gene therapy for haemophilia B using primary human keratinocytes. Nat Genet 1993;3:180-3.  Back to cited text no. 35  [PUBMED]  [FULLTEXT]  
36.Meng X, Sawamura D, Tamai K, Hanada K, Ishida H, Hashimoto I. Keratinocyte gene therapy for systemic disease. Circulating interleukin 10 released from gene transferred keratinocytes inhibits contact hypersensitivity at distant areas of the skin. J Clin Invest 1998;101:1462-7.  Back to cited text no. 36  [PUBMED]  [FULLTEXT]  
37.Cao T, Wang XJ, Roop DR. Regulated cutaneous gene delivery: The skin as a bioreactor. Hum Gene Ther 2000;11:2297-300.  Back to cited text no. 37  [PUBMED]  [FULLTEXT]  
38.Katz AB, Taichman LB. A partial catalogue of proteins secreted by epidermal keratinocytes in culture. J Invest Dermatol 1999;112:818-21.  Back to cited text no. 38  [PUBMED]  [FULLTEXT]  
39.Meng X, Sawamura D, Ina S, et al . Keratinocyte gene therapy: Cytokine gene expression in local keratinocytes and in circulation by introducing cytokine genes into skin. Exp Dermatol (in press).   Back to cited text no. 39      
40. Dunlap S, Yu X, Cheng L, Civin CI, Alani RM. High efficiency stable gene transduction in primary human melanocytes using a lentiviral expression system. J Invest Dermatol 2004;122:549-51  Back to cited text no. 40      
41.Mathor MB, Ferrari G, Dellambra E, Cilli M, Mavilio F, Cancedda R, et al . Clonal analysis of stably transduced human epidermal stem cells in culture. Proc Natl Acad Sci USA 1996;93:10371-6.  Back to cited text no. 41      
42.Mullen CA, Snitzer K, Culver KW, Morgan RA, Anderson WF, Blaese RM. Molecular analysis of T lymphocyte-directed gene therapy for adenosine deaminase deficiency: Long-term expression in vivo of genes introduced with a retroviral vector. Hum Gene Ther 1996;7:1123-9.  Back to cited text no. 42  [PUBMED]    
43.Vogel JC. Keratinocyte gene therapy. Arch Deramtol 1993;129:1478-83.  Back to cited text no. 43  [PUBMED]    
44.Terron A, McLean WH. Ribozyme gene therapy for keratin disorders. Acta Derm Venereol 2001;81:237.  Back to cited text no. 44      
45.D'Alessandro M, Morley SM, Ogden PH, Liovic M, Porter RM, Lane EB. Functional improvement of mutant keratin cells on addition of desmin: An alternative approach to gene therapy for dominant diseases. Gene Ther 2004;11:1290-5.  Back to cited text no. 45      
46.Ferrari S, Pellegrini G, Matsui T, Mavilio F, De Luca M Gene therapy in combination with tissue engineering to treat epidermolysis bullosa. Exp Opin Biol Ther 2006;6:367-78.  Back to cited text no. 46      
47.Ortiz-Urda S, Lin Q, Yant SR, Keene D, Kay MA, Khavari PA. Sustainable correction of junctional epidermolysis bullosa via transposon-mediated nonviral gene transfer. Gene Ther 2003;10:1099-104.  Back to cited text no. 47  [PUBMED]  [FULLTEXT]  
48.Robbins PB, Lin Q, Goodnough JB, Tian H, Chen X, Khavari PA. In vivo restoration of laminin 5 beta 3 expression and function in junctional epidermolysis bullosa. Proc Natl Acad Sci USA 2001;98:5193-8.  Back to cited text no. 48  [PUBMED]  [FULLTEXT]  
49.Seitz CS, Giudice GJ, Balding SD, Marinkovich MP, Khavari PA. BP180 gene delivery in junctional epidermolysis bullosa. Gene Ther 1999;6:42-7.  Back to cited text no. 49  [PUBMED]  [FULLTEXT]  
50.Goto M, Sawamura D, Ito K, Abe M, Nishie W, Sakai K, et al . Fibroblast show more potential as target cells than keratinocytes in COL7A1 gene therapy of dystrophic epidermolysis bullosa. J Invest Dermatol 2006;126:766-72.  Back to cited text no. 50      
51.Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature 2001;411:366-74.  Back to cited text no. 51  [PUBMED]  [FULLTEXT]  
52.Costa RM, Chigancas V, Galhardorda S, Carvalho H, Menck CF. The eukaryotic nucleotide excision repair pathway. Biochimie 2003;85:1083-99.  Back to cited text no. 52      
53.Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH, et al . In vivo gene delivery and stable transduction of non-dividing cells by a lentiviral vector. Science 1996;272:263-7.  Back to cited text no. 53      
54.Marchetto MC, Correa RG, Menck CF, Muotri AR. Functional lentiviral vectors for xeroderma pigmentosum gene therapy. J Biotechnol 2006 [Epub ahead of print].  Back to cited text no. 54      
55.Carreau M, Quillet X, Eveno E, Salvetti A, Danos O, Heard JM, et al . Functional retroviral vector for gene therapy of Xeroderma group B patients. Hum Gene Ther 1995;6:1308-15.  Back to cited text no. 55      
56.Choate KA, Kinsella TM, Wiliams ML, Nolan GP, Khavari PA. Transglutaminase 1 delivery to lamellar ichthyosis keratinocytes. Hum. Gene Ther 1996;7:2247-53.  Back to cited text no. 56      
57.Choate KA, Medalie DA, Morgan JR, Khavari PA. Corrective gene transfer in the human skin disorder lamellar ichthyosis. Nat Med 1996;2:1263-7.  Back to cited text no. 57  [PUBMED]    
58.Andree C, Swain WF, Page CP, Macklin MD, Slama J, et al . In vivo transfer and expression of a human epidermal growth factor gene accelerates wound repair. Proc Natl Acad Sci USA 1994;91:12188-92.  Back to cited text no. 58      
59.Tyrone JW, Mogford JE, Chandler LA, Ma C, Xia Y, Pierce GF, et al . Collagen-embedded platelet-derived growth factor DNA plasmid promotes wound healing in a dermal ulcer model. J Surg Res 2000;93:230-6.   Back to cited text no. 59      
60.Liechty KW, Nesbit M, Herlyn M, Radu A, Adzick NS, Crombleholme TM. Adenoviral-mediated overexpression of platelet-derived growth factor-B corrects ischemic impaired wound healing. J Invest Dermatol 1999;113:375-83.  Back to cited text no. 60  [PUBMED]  [FULLTEXT]  
61.O'Malley BW Jr, Chen SH, Schwartz MR, Woo SL. Adenovirus-mediated gene therapy for human head and neck squamous cell cancer in a nude mouse model. Cancer Res 1995;55:1080-5.  Back to cited text no. 61      

This article has been cited by
1 Evaluation of signal transduction pathways after transient cutaneous adenoviral gene delivery
Steinstraesser, L., Sorkin, M., Jacobsen, F., Al-Benna, S., Kesting, M.R., Niederbichler, A.D., Otte, J., (...), Schulte, M.
BMC Immunology. 2011; 12(art 8)
2 Genes and gene therapy
Iftikhar, U., Kazmi, A.H.
Journal of the College of Physicians and Surgeons Pakistan. 2011; 21(6): 323-324
3 Evaluation of signal transduction pathways after transient cutaneous adenoviral gene delivery
Lars Steinstraesser, Michael Sorkin, Frank Jacobsen, Sammy Al-Benna, Marco Rainer Kesting, Andreas David Niederbichler, Jan-Michel Otte, Tobias Hirsch, Jadwiga Stupka, Hans-Ulrich Steinau, Matthias Schulte
BMC Immunology. 2011; 12(1)
[Pubmed] | [DOI]
4 Genetic engineering-trends in drug development
Nanjawade, B.K., Suryadevara, K., Sushmitha, S., Kella, M.
Current Trends in Biotechnology and Pharmacy. 2010; 4(3): 736-745


Print this article  Email this article
   Next article
   Previous article 
   Table of Contents
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Article in PDF (469 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

    Hybrid Methods
    Immune Reaction
    Gene therapy in ...
    Gene therapy in ...
    Inherited Skin D...
    Xeroderma pigmen...

 Article Access Statistics
    PDF Downloaded1112    
    Comments [Add]    
    Cited by others 4    

Recommend this journal