gene therapy in periodontics

1. GOOD AFTERNOON

2. GENE MAGIC IN
PERIODONTOLOGY!!
Presentation code : CRS1628

3. CONTENTS:
 INTRODUCTION
 HISTORY
 FUNDAMENTALS
 TYPES OF GENE THERAPY
 GENE DELIVERY
 IMPLICATIONS
 TISSUE ENGINEERING
 APPLICATIONS
 LIMITATIONS
 CONCLUSION

4. INTRODUCTION:
 A broad definition of gene therapy is the genetic
modification of cells for therapeutic purposes.
 It involves the transfer of a therapeutic or working gene
copy into specific cells of an individual in order to repair a
faulty gene copy, which is to cure or to favorably modify
the clinical course of a condition. It has a promising era in
the field of periodontics.
 Periodontal diseases, have a broad spectrum of
inflammatory and destructive responses, and are thought
to be multi-factorial in origin.

5. HISTORY:
 In the mid 1980s, the focus of gene therapy was entirely
on treating diseases caused by single gene defects.
 The first gene therapy trials on humans began in 1990 on
patients with Severe Combined Immunodeficiency (SCID).
 In 2000, the first gene therapy "success" resulted in SCID
patients with a functional immune system.

6. FUNDAMENTALS:
There are different methods to replace or repair the genes
targeted in gene therapy.
 A normal gene may be inserted into a nonspecific
location within the genome to replace a nonfunctional
gene. This approach is most common.
 An abnormal gene could be swapped for a normal gene
through homologous recombination.
 The abnormal gene could be repaired through selective
reverse mutation, which returns the gene to its normal
function.

7. FUNDAMENTALS:
 The regulation (the degree to which a gene is turned on
or off) of a particular gene could be altered.
 The Spindle transfer is used to replace entire
mitochondria that carry defective mitochondrial DNA.

8. TYPES OF GENE THERAPY:
Classified into two types
 GERM LINE GENE THERAPY:
Germ cells, i.e., sperm or eggs are modified by the
introduction of functional genes, which are
ordinarily integrated into their genomes. Heritable
 SOMATIC GENE THERAPY:
The therapeutic genes are transferred into the somatic
cells. Inheritable

9. GENE DELIVERY:
Gene delivery is done by using
Viral vectors and
Non viral vectors
Direct delivery/viral vectors:
 Retroviruses
 Adenoviruses
 Adeno-associated viruses
 Herpes simplex viruses
 Vaccina viruses
 Pox viruses
 Lenti viruses

10. Gene delivery:
Non viral/cell based delivery:
 Micro seeding gene therapy
 Cationic liposomes
 Macromolecular conjugate
 Gene activated matrices(GAMS)
 Experiments with the introduction of a 47th chromosome
(artificial, human techno-chromosome) into target cells
are being carried out.

12. IMPLICATIONS IN PERIODONTICS
Approaches for regenerating tooth-supporting structures
 (A) Guided tissue regeneration uses a cell occlusive
barrier membrane to restore periodontal tissues.
 (B) Alternatively, an example of gene therapy uses
vector-encoding growth factors aimed at stimulating the
regeneration of host cells derived from the periodontium.

14. TISSUE ENGINEERING:

15.  There are three approach of tissue engineering in
periodontics:
1. Protein based approach:
Growth and differentiation factors are used for
regeneration of periodontal tissues like TGF-β,
BMP-2,6,7,12, bFGF, VEGF and PDGF.
2. Cell based approach:
using mesenchymal stem cells.

16. 3. Gene delivery approach:
Gene vectors can be introduced directly to the target
site (in vivo technique) or selected cells can be harvested,
expanded,genetically transduced, and then reimplanted
(ex vivo technique).

17. IN VIVO:
Gene therapy is done by targeting the gene delivery
system to the desired cell type in the patient using either
physical means such as:
1. Tissue injection (brain tumor) or
2. Biolistics (dermal DNA vaccination),
3. Systemic infusion of cell-specific receptor-mediated
DNA carriers (reconstructed liposome’s or viruses).

18. EX VIVO:
Ex-vivo gene therapy is performed by transfecting or
infecting patient-derived cells in culture with vector DNA
and then reimplanting the transfected cells into the patient.
Two types of ex-vivo gene therapies under development are
those directed at fibroblasts and hematopoietic stem cells .

20. APPLICATIONS IN
PERIODONTOLOGY

21. Gene therapeutics-periodontal vaccination:
 Using plasmid DNA encoding the Porphyromonas gingivalis
fimbrial gene resulted in the subsequent production of specific
salivary IgA and or IgG, antibodies and serum IgG antibodies. This
secreted IgA could neutralize P. gingivalis and limit its ability to
participate in plaque formation.
 With genetically engineered Strepto-cocci gordoni vectors
expressing P. gingivalis fimbrial antigen can be used as vaccine
against P. gingivalis associated periodontitis.
 Protection against P. gingivalis induced bone loss.

22. 2. Genetic approach to biofilm antibiotic resistance:
 Bacteria growing in biofilms become up to 1,000 fold more
resistant to antibiotics as compared to a planktonic
counterpart making them hard to control.
 Gene ndvB encoding for glycosyltransferase is required for
the synthesis of periplasmic glucans in wild form of
Pseudomonas aeuroginosa RA14 strain.
 Isolation of ndvB mutant of Pseudomonas aeuroginosa was
still capable of forming biofilm but lacked the characteristic of
periplasmic glucans there by rendering microbial
communities in biofilm more susceptible to conventional
antibiotic therapy.

23. Genetic approach to antibiotic resistance

24. 3.An In-vivo gene transfer by Electroporation for
Alveolar Remodeling:
LacZ gene encoding for remodeling molecules

25. 4.Antimicrobial gene therapy to control disease
progression
 One way to enhance host defense mechanism against
infection is by transfecting host cells with an antimicrobial
peptide/protein- encoding gene.
 When host cells were infected in vivo with β defensin-2
(HBD-2) gene via retroviral vector;there was a potent
antimicrobial activity which enhanced host antimicrobial
defenses.

26. 5. Designer drug therapy in treating periodontal disease:
 If genes necessary for normal development are known,
then "designer drug therapies" aimed at one area of the
gene or the other can be developed.
 Safer than today′s medicines because they would only
affect the defect in a gene clearly identified through
genetic research.

27. Future strategies of gene therapy:
 Tight Adherence Gene for the Control of
Periodontal Disease Progression.
 Gene Therapy to Grow New Teeth.

28. Limitations of Gene Therapy
 1. Short-lived nature of gene therapy.
 2. Immune response of the patient.
 3. Problems with viral vectors like patient toxicity,
immune and inflammatory responses, and gene
control and targeting issues.
 4. Limitation of sufficient quantity of the
engineered gene that can be delivered.
 5. Extreme cost.
 6. Ethical restrictions.

29. Conclusion:
 Gene therapy has a promising role in the field of
periodontics but it does encompass serious ethical issue
to be dealt with.
 Since gene transfer tools are in their infancy, it is not
likely gene transfer approaches will be used for routine
periodontal care on humans.
 There are still lots of research and details of mechanisms
to be understood to include these practically in day to
day treatment modalities.

30. References:
 Review article- Gene therapy in periodontics-Department of
Periodontics,Institute of Dental Sciences, Bareilly,Uttar Pradesh, India
Anirban Chatterjee, Nidhi Singh, Mini Saluja
 Gene therapy and its implications in Periodontics
Swapna Mahale, Nitin Dani1, Shumaila S. Ansari2, Triveni Kale3
 Gene therapy in periodontology:A Review and future implications
The Journal of contemporary dental practice,volume 7,No.3,july1,2006
B.V.kathikeyan,A.R.Pradeep
 Gene therapy in periodontics
Anirban Chatterjee, Nidhi Singh, Mini Saluja

31. Thank you