International Journal of Oral & Maxillofacial Pathology. 2012;3(3):65-67 ISSN 2231 – 2250

Available online at http://www.journalgateway.com or www.ijomp.org

Brief Communication

Dental Surgeons as Gene Therapist

Paramel Mohan Sunil, Ramachandran CR, Jaisanghar N, Santhosh Kumar C

Abstract

Gene therapy is a particular method by which defective gene is replaced or repaired by therapeutic gene. Vectors are vehicles which deliver the therapeutic gene into the host. Gene therapy can be used to treat wide range of diseases ranging from single gene disorder to m ulti- gene disorder. In dentistry the application of gene therapy includes bone repair, for treating auto immune disease, pain, DNA vaccination (for caries and periodontal disease) and cancer. Minor salivary glands and keratinocytes present in the oral mucosa are the excellent target sites for gene therapy since it can be readily accomplished with minimal invasive manner. This makes dentists as suitable candidate for gene therapy.

Keywords: Therapy;Gene;DNA;Somatic;Genetic Services;Biological Therapy;Vaccination; Immunotherapy;Oral Cancer;Vector.

Paramel Mohan Sunil, Ramachandran CR, Jaisanghar N, Santhosh Kumar C. Dental Surgeons as Gene Therapist. International Journal of Oral and Maxillofacial Pathology; 2012:3(3):65-67. ©International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved.

Received on: 24/02/2012 Accepted on: 09/07/2012

Introduction

Rapid progress in molecular biological technology has made researchers to manipulate gene easier. A gene is a linear sequence of DNA that codes for a particular protein. Gene therapy is a technique in which defective genes that are responsible for disease development are corrected. The applications of gene therapy are based on the principle that a normal gene is inserted to compensate for a non functional gene and abnormal gene that can be repaired through selective reverse mutation. Scientists began gene therapy with bacteria in 1980 and first gene therapy in human (1990) was performed for treating severe combined immunodeficiency which worked for only few months. Gene therapy in recent days has grown by leaps and bounds and its application in dentistry includes bone repair, treatment of salivary gland diseases, auto immune diseases, pain, DNA vaccination,
dermatological disorder and cancer1.

Principles of Gene Therapy

Gene therapy is a technique in which normal gene is inserted in to host for a non- functional and abnormal gene, which are repaired through selective reverse mutation. The procedure involved in gene therapy includes
a. Pinpoint gene of interest,
b. Acquiring a normal copy of gene (therapeutic gene) by restrictive endonuclease enzyme (cutting and splicing) and
c. Finally cloning of therapeutic gene into a vector, which is a vehicle to deliver the gene of interest.
Vector delivers the therapeutic gene into patient’s target. The target cells become infective with therapeutic gene through vector. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage 2.

Requirements for Vector3

The ideal requirements for vectors are
a) It should not be identified by immune system (non-immunologic)
b) Should be stable and easy to reproduce and
c) Should have longevity of expression.

Types of Vector3

Vectors can be either Viral or Non-Viral.

1. Commonly used viral vectors are Adeno virus, Adeno associated virus, Retro virus and Herpes virus. Among these, adenovirus is commonly used, as it can be cultured easily and because of its lower pathogenicity.

2. Non-Viral options include,

a. Direct introduction of therapeutic
DNA - Disadvantage being it can be used only with certain tissue and requires a lot of DNA,
b. Creation of artificial lipid sphere with aqueous core, liposome - Carries therapeutic DNA through membrane,

©2012 International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited . All Rights Reserved

66 Sunil PM et al., ISSN 2231 - 2250

c. Chemically linking DNA to molecule that will bind to special cell receptors - Less effective and
d. Trying to introduce a 47th chromosome; could carry a lot of information.

Types of Gene Therapy4

1. Germ line gene therapy: Repair or
replace defective gene in germ line cell. Modified gene would be inherited.
2. Somatic gene therapy: Repair or
replace defective gene in some or all body cells of an individual.

Types of delivery

a) In vivo: delivery of gene takes place in the body.
b) Ex vivo: delivery takes place outside
the body and the cells are placed back in to the body.

Applications in Dentistry

Bone repair: Bone defects in the oral and maxillofacial region can be repaired by transferring genes encoding BMP’s (Bone morphogenic Protein).It will be possible to directly deliver the BMP-2 gene in vivo to tissues via an adeno viral

vector to heal bone defects5. Michigan research group has found non osteogenic fibroblasts (gingiva, dental pulp), which can express BMP-7 gene after being infected with an adeno viral
vector6.

Pain: Managing or eliminating pain is a major part of dental practice. The use of

gene transfer technology offers a potentially novel approach to manipulate
specific, localized biochemical pathways involved in pain generation. Gene
transfer may be particularly useful for managing chronic and intractable pain.

DNA Vaccination: Dental scientists have tried to use classical vaccination technology to eradicate dental caries or periodontal diseases, thus far achieving

mixed success. Applications of DNA
vaccination are in the earliest stages of its use with oropharyngeal tissues. DNA vaccination will play a role in future strategies for preventing periodontal diseases and dental caries.

Keratinocyte: Keratinocyte are the cells which are present in oral mucosa.

Several features make epidermal and mucosal keratinocytes, attractive for
treating local tissue disorders and as systemic gene therapeutics.8 Expression
of therapeutic genes can be achieved with use of topically applied agents. Gene therapy can be used to treat keratinocytes disorder like ichthyosis and epidermolysis bullosa. In future it can be used to treat most of
dermatologic disorders.9
Oral Cancer: The general strategy in cancer treatment is to express a gene product that will result in cancer cell death.7 It can be achieved by
1. Addition of a tumor-suppressor gene
(gene addition therapy);
2. Deletion of a defective tumor gene
(gene excision therapy);
3. Down-regulation of the expression of genes that stimulate tumor growth;
4. Enhancement of immune surveillance
(immunotherapy);
5. Activation of pro-drugs that have a chemotherapeutic effect ("suicide" gene therapy);
6. Introduction of genes to inhibit tumor angiogenesis.

Dental surgeon as Gene Therapist

To conclude, the role of dental surgeon in gene therapy is tenable. Dental surgeon has got easy approach to areas like salivary glands and keratinocytes (oral epithelium). Salivary glands are excellent target sites for gene transfer, readily accomplished in minimal invasive manner. There are about
500-1000 minor salivary gland in oral cavity. Salivary gland produce large amount of proteins and it is a site where gene transfer can be readily accomplished in minimal
invasive manner.8 Salivary glands could be used for gene therapeutic applications with single protein deficiencies. Irreversible salivary gland dysfunction due to
autoimmune diseases9 and irradiation can
also be corrected using GT. Keratinocyte are the cells which are present in oral mucosa. Several features make epidermal and mucosal keratinocytes, attractive for treating local tissue disorders and as systemic gene
therapeutics.9 Expression of therapeutic genes can be achieved with use of topically applied agents. Gene therapy can be used to treat disorders of keratinocytes like ichthyosis and epidermolysis bullosa. In future it can be used to treat most of
dermatologic disorders.10
Dental surgeon can be the best fitting professional to administer gene therapy in the oral cavity which bears minor salivary glands and keratinocytes. Patient with intractable pain in any part of the body can

ISSN 2231 – 2250 Dental Surgeons as Gene Therapist... 67

walk in to dental clinic to get his/her pain relieved through gene therapy. In future dentist will have inseparable role in the field of gene therapy.

Author Affiliation

1. Dr.Sunil PM, Professor and Head, RMDC & H, Annamalai University, 2. Dr.Ramachandran CR, Professor and Head, Department of Oral Pathology, VDC & H, Bhimavaram, 3. Dr.Jaisanghar N, Professor, Department of Oral Medicine, RMDC & H, Annamalai University, 4. Dr.Santhosh Kumar C, Reader, Department of Oral Pathology, SRDC & H, Coimbatore, India.

Acknowledgement

We would like to thank all the staff members from Department of Oral Pathology and Oral Medicine for their support & cooperation.

References

1. Bruce J. Baum, Mark Kok, Simon D.
Tran, Sehchi Yamano. The impact of gene therapy on dentistry. JADA
2002;133:35-43.
2. 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. Nucleic Acids Res
2005:33(18):5978–90.
3. Kay MA, Glorioso JC, Naldini L. Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat Med 2001;7:33–40.
4. Baum BJ, O’Connell BC. The impact of
gene therapy on dentistry. JADA
1995;126:179–89.
5. Franceschi RT, Wang D, Krebsbach PH, Rutherford RB. Gene therapy for bone formation: in vitro and in vivo osteogenic activity of an adenovirus expressing BMP7. J Cell Biochem 2000;78:476–86.
6. Krebsbach PH, Gu K, Franceschi RT, Rutherford RB. Gene therapy-directed osteogenesis: BMP-7-transduced human fibroblasts form bone in vivo. Hum Gene Ther 2000;11:1201–10.
7. Heise C, Sampson-Johannes A, Williams A, McCormick F, Von Hoff DD, Kirn DH. ONYX-015, an E1B gene- attenuated adenovirus, causes tumor- specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med 1997;3:639–45.
8. Barka T, Van der Noen HM. Retrovirus- mediated gene transfer into salivary glands in vivo. Hum Gene Ther
1996;7:613–8.
9. Tsokos GC, Nepom GT. Gene therapy in the treatment of autoimmune diseases. J Clin Invest 2000;106:181–3.
1 0 . Khavari PA. Genetic correction of inherited epidermal disorders. Hum Gene Ther 2000;11:2277–82.

Corresponding Author Dr.Sunil PM, MDS, PhD Professor and Head, Department of Oral Pathology,

RMDC & H, Annamalai University, Annamalai Nagar, Chidambaram-608002

Email: sunilnarien@gmail.com

Source of Support: Nil, Conflict of Interest: None Declared.


Fatal error: Call to a member function getRouter() on null in /home/journalg/public_html/lib/pkp/classes/template/PKPTemplateManager.inc.php on line 71