GENE THERAPY IN AIDS

1. GENE THERAPY IN AIDS PRESENTED BY PAIROAJ VONGHATHAIPAISARN MASTER DEGREE STUDENT OF MAHIDOL UNIVERSITY

2. CONTENT -INTRODUCTION -GENE THERAPY IN MEDICINE -GENE THERAPY IN AIDS -GENE DELIVERY -CONCLUSION

3. GENE THERAPY IS A TREATMENT OR PREVENTION OF DISEASE BY GENE TRANSFER EDWARD TATUM GIVE THIS CONCEPT SINCE 1966

4. GENE THERAPY IN MEDICINE -POTENTIAL REVOLUTION IN MECICINE -AIMED AT TREATING OR ELIMINATING THE CAUSES OF DISEASE

5. GENE THERAPY IN MEDICINE -ORIGINALLY WAS ENVISIONED AS A MEANS TO TREAT DISEASES ARISING FROM SINGLE GENE DEFECTS -FAILURE TO SYNTHESIZE A PARTICULAR PROTEIN OR TO SYNTHESIS OFF AN ABNORMAL PROTEIN

6. GENE THERAPY IN MEDICINE -NOW GENE THERAPY ADAPT TO USE IN ACQUIRED DISEASE SUCH AS AIDS, MALIGNANCIES AND CARDIOVASCULAR DISEASE -GENE THERAPY FOR ACQUIRED DISEASE HAS PROCEEDED FASTER THAN FOR INHERITED DISORDER

7. GENE THERAPY IN MEDICINE -THE EARLIEST HUMAN GENE TRANSFER EXPERIMENTS BEGAN IN 1989 -NO THERAPEUTIC EFFECT -SHOWED ONLY SAFETY AND MANY OF TECHNICAL DIFFICULTIES

8. GENE THERAPY IN AIDS -TODAY, DRUG THERAPY IN AIDS ONLY CONTROL NOT CURE DISEASE -ADMINISTRATION SCHEDULES -SIGNIFICANT TOXICITY -SO CONTINUING NEED FOR NEW OR INNOVATIVE THERAPIES INCLUDING GENE THERAPY

9. GENE THERAPY IN AIDS 1.INTRACELLULAR IMMUNIZATION 2.RIBOZYMES 3.TRANSDOMINANT MUTANT 4.TROJAN HORSE

10. THE HIV LIFE CYCLE AND POINTS OF INTERVENTION 1.TAT -KEY PLAYER IN THE EARLY STAGES OF HIV RNA SYNTHESIS 2.REV -SECOND KEY REGULATOR CAUSES SHIFT IN THE TYPE OF HIV m RNA PRODUCE TO LONGER TRANSCRIPTS

11. BINDING REGION ON TO HIV m RNA -TAT---> TAR (TRANS-ACTIVATION RESPONSE-ELEMENT) -REV-----> RRE (REV-RESPONSE ELEMENT ) *TAT + TAR -->> POTENT ACTIVATION OF VIRAL GENE EXPRESSION BY INDUCING TRANSCRIPTIONAL INITIATION AND ELONGATION *REV + RRE -->> STRONG ACTIVATES HIV BY FACILITATING THE EXTRACELLULAR TRANSPORT OF UNSPLICED OR SINGLY SPLICED m RNA

12. RHIBOZYME RHIBOZYME ARE RNA MOLECULES THAT CONTAIN ANTISENSE SEQUENCE FOR SPECIFIC RECOGNITION AND A RNA-CLEAING ENZYMATIC ACTIVITY

13. SEVERAL FEATURES OF RZs MAKE THEM ATTRACTIVE FOR HIV GENE THERAPY -SIMPLICITY OF DESIGN -LACK OF IMMUNOGENICITY OF RNA -POSSIBILITY OF DESIGNING MULTIPLE RZS AGAINST CONSERVED REGION OF VIRAL GENOME

14. TWO TYPE OF RZS THAT HAVE BEEN USED MOST EXTENSIVELY ARE HAIRPIN AND HAMMERHEAD

16. HAIRPIN Rz REQUIRING A GUC AT THE CLEVAGE SITE HAMMERHEAD Rz REQUIRING A NUH (WHERE “N” DENOTES ANY BASE AND “H” DENOTES A, C OR U)

17. RHIBOZYME APPLICATION IN AIDS TAGET RNA : HIV -I Rz TYPE : HAIRPIN HAMMERHEAD MODE OF DELIVERY AND RESULTING PHENOTYPE : RETROVIRUS DELIVERY OF A VARIETY OF HIV Rzs : INHIBITOR VIRAL REPLICATION 10-1000 FOLD IN T-CELL, T-CELL LINES AND CD34 STEM CELL PROGENY

18. TROJAN HORSE IS AN ANTI-HIV RNA THAT CONTAINS AN HIV-PACKAGING SIGNAL COUPLED TO AN ANTI-HIV NUCLEIC ACID.

19. TRANS-DOMIANAT MUTANT (PROTEIN) TRANSDOMINAT PROTEIN ARE PROTEINS THAT HAVE ALTERED AMINO ACID THAT RENDER THE MUTANT PROTEIN CAPABLE OF DISRUPTING THE FUNCTIONS OF THE WILD-TYPE PROTEIN LTR CMVIE REV M10 LTR

20. REGULARTORY PROTEIN : TAT, REV STRUCTURAL PROTEIN : Gag AND Env (PREVENT LIBERATION OF VIRION OR LEAD TO THE RELEASE OF DEFECTIVE PARTICLES THAT CANNOT INFECT NEW TARGET CELLS

21. INTRACELLULAR IMMUNIZATION (INTRABODIES) INTRABODY : AN ANTIBODY THAT IS PRODUCED INTRACELLULARY BY GENETIC ENGINEERING TO MAKE THE ENGINEERED CELLS RESISTANT TO VIRAL INFECTION

22. THESE ARE Ig - DERIVED MOLECULES THAT COMBINE HIV-SPECIFIC VARIABLE REGIONS WITH AN ALTERED IMMUNOGLOBULINE CONSTANT REGION DOMAIN THAT RESULTS IN THE MOLECULES BEING RETAINED INSIDE THE CELL.

23. INTRABODIES AGAINST : TAT, REV, REVERSE TRANSCRIPTASE AND ENVELOPE EPITOPE

24. ANOTHER FORM : RNA DECOY , SUICIDE GENE, ANTISENSE NEUCLEIC ACID

26. GENE DELIVERY -VIRAL VECTOR -NON VIRAL VECTOR

30. CONCLUSION THANK YOU VERY MUCH