Therapeutic Nucleic Acids

  • Mauro Giacca


As introduced in the previous chapter, the term “gene therapy” refers to a vast series of applications, both in vivo and ex vivo, based on the utilization of nucleic acids for therapeutic purposes.


Gene Therapy Long Terminal Repeat Duchenne Muscular Dystrophy Triple Helix Peptide Nucleic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

2.1 Protein-Coding Genes

Further Reading

  1. Baron U, Bujard H (2000) Tet repressor-based system for regulated gene expression in eukaryotic cells: principles and advances. Methods Enzymol 327:401–421CrossRefPubMedGoogle Scholar
  2. Brown BD, Naldini L (2009) Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat Rev Genet 10:578–585CrossRefPubMedGoogle Scholar
  3. Clackson T (1997) Controlling mammalian gene expression with small molecules. Curr Opin Chem Biol 1:210–218CrossRefPubMedGoogle Scholar
  4. Duca M, Vekhoff P, Oussedik K et al (2008) The triple helix: 50 years later, the outcome. Nucleic Acids Res 36:5123–5138CrossRefPubMedGoogle Scholar
  5. Guo ZS, Li Q, Bartlett DL, Yang JY, Fang B (2008) Gene transfer: the challenge of regulated gene expression. Trends Mol Med 14:410–418CrossRefPubMedGoogle Scholar
  6. Harvey DM, Caskey CT (1998) Inducible control of gene expression: prospects for gene therapy. Curr Opin Chem Biol 2:512–518CrossRefPubMedGoogle Scholar
  7. Lobato MN, Rabbitts TH (2003) Intracellular antibodies and challenges facing their use as therapeutic agents. Trends Mol Med 9:390–396CrossRefPubMedGoogle Scholar
  8. Magnenat L, Schwimmer LJ, Barbas CF (2008) Drug-inducible and simultaneous regulation of endogenous genes by single-chain nuclear receptor-based zinc-finger transcription factor gene switches. Gene Ther 15:1223–1232CrossRefPubMedGoogle Scholar
  9. Muyldermans S, Cambillau C, Wyns L (2001) Recognition of antigens by single-domain antibody fragments: the superfluous luxury of paired domains. Trends Biochem Sci 26:230–235CrossRefPubMedGoogle Scholar
  10. Toniatti C, Bujard H, Cortese R, Ciliberto G (2004) Gene therapy progress and prospects: transcription regulatory systems. Gene Ther 11:649–657CrossRefPubMedGoogle Scholar

Selected Bibliography

  1. Baum C, Margison GP, Eckert H-G et al (1996) Gene transfer to augment the therapeutic index of anticancer chemotherapy. Gene Ther 3:1–3PubMedGoogle Scholar
  2. Brown BD, Gentner B, Cantore A et al (2007) Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state. Nat Biotechnol 25:1457–1467CrossRefPubMedGoogle Scholar
  3. Gossen M, Bujard H (1992) Tight control of gene expression in mammalian cells by tetracyclineresponsive promoters. Proc Natl Acad Sci USA 89:5547–5551CrossRefPubMedGoogle Scholar
  4. Lobato MN, Rabbitts TH (2003) Intracellular antibodies and challenges facing their use as therapeutic agents. Trends Mol Med 9:390–396CrossRefPubMedGoogle Scholar
  5. Meyer-Ficca ML, Meyer RG, Kaiser H et al (2004) Comparative analysis of inducible expression systems in transient transfection studies. Anal Biochem 334:9–19CrossRefPubMedGoogle Scholar
  6. No D, Yao TP, Evans RM (1996) Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc Natl Acad Sci USA 93:3346–3351CrossRefPubMedGoogle Scholar
  7. Weber W, Fussenegger M (2006) Pharmacologic transgene control systems for gene therapy. J Gene Med 8:535–556CrossRefPubMedGoogle Scholar

Non-Coding Nucleic Acids Further Reading

  1. Brown BD, Naldini L (2009) Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat Rev Genet 10:578–585CrossRefPubMedGoogle Scholar
  2. Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136:642–655CrossRefPubMedGoogle Scholar
  3. Castanotto D, Rossi JJ (2009) The promises and pitfalls of RNA-interference-based therapeutics. Nature 457:426–433CrossRefPubMedGoogle Scholar
  4. Duca M, Vekhoff P, Oussedik K et al (2008) The triple helix: 50 years later, the outcome. Nucleic Acids Res 36:5123–5138CrossRefPubMedGoogle Scholar
  5. Dykxhoorn DM, Palliser D, Lieberman J (2006) The silent treatment: siRNAs as small molecule drugs. Gene Ther 13:541–552CrossRefPubMedGoogle Scholar
  6. Fichou Y, Férec C (2006) The potential of oligonucleotides for therapeutic applications. Trends Biotechnol 24:563–570CrossRefPubMedGoogle Scholar
  7. Hannon GJ (2002) RNA interference. Nature 418:244–251CrossRefPubMedGoogle Scholar
  8. Opalinska JB, Gewirtz AM (2002) Nucleic-acid therapeutics: basic principles and recent applications. Nat Rev Drug Discov 1:503–514CrossRefPubMedGoogle Scholar
  9. Que-Gewirth NS, Sullenger BA (2007) Gene therapy progress and prospects: RNA aptamers. Gene Ther 14:283–291CrossRefPubMedGoogle Scholar
  10. Rao DD, Vorhies JS, Senzer N, Nemunaitis J (2009) siRNA vs. shRNA: similarities and differences. Adv Drug Deliv Rev 61:746–759CrossRefPubMedGoogle Scholar
  11. Ryther RC, Flynt AS, Phillips JA 3rd, Patton JG (2005) siRNA therapeutics: big potential from small RNAs. Gene Ther 12:5–11CrossRefPubMedGoogle Scholar
  12. Shi Y (2003) Mammalian RNAi for the masses. Trends Genet 19:9–12CrossRefPubMedGoogle Scholar
  13. Sioud M, Iversen PO (2005) Ribozymes, DNAzymes and small interfering RNAs as therapeutics. Curr Drug Targets 6:647–653CrossRefPubMedGoogle Scholar
  14. Stevenson M (2004) Therapeutic potential of RNA interference. N Engl J Med 351:1772–1777CrossRefPubMedGoogle Scholar
  15. Tuschl T (2002) Expanding small RNA interference. Nat Biotechnol 20:446–448CrossRefPubMedGoogle Scholar
  16. Wagner RW (1994) Gene inhibition using antisense oligodeoxynucleotides. Nature 372:333–335CrossRefPubMedGoogle Scholar
  17. Wall NR, Shi Y (2003) Small RNA: can RNA interference be exploited for therapy? Lancet 362:1401–1403CrossRefPubMedGoogle Scholar
  18. Zentilin L, Giacca M (2004) in vivo transfer and expression of genes coding for short interfering RNAs. Curr Pharm Biotechnol 5:341–347CrossRefPubMedGoogle Scholar

Selected Bibliography

  1. Bertrand E, Castanotto D, Zhou C et al (1997) The expression cassette determines the functional activity of ribozymes in mammalian cells by controlling their intracellular localization. RNA 3:75–88PubMedGoogle Scholar
  2. Brummelkamp TR, Bernards R, Agami R (2002) A system for stable expression of short interfering RNAs in mammalian cells. Science 296:550–553CrossRefPubMedGoogle Scholar
  3. de Fougerolles AR (2008) Delivery vehicles for small interfering RNA in vivo. Hum Gene Ther 19:125–132CrossRefPubMedGoogle Scholar
  4. Dollins CM, Nair S, Sullenger BA (2008) Aptamers in immunotherapy. Hum Gene Ther 19:443–450CrossRefPubMedGoogle Scholar
  5. Fedor MJ (2000) Structure and function of the hairpin ribozyme. J Mol Biol 297:269–291CrossRefPubMedGoogle Scholar
  6. Gleave ME, Monia BP (2005) Antisense therapy for cancer. Nat Rev Cancer 5:468–479CrossRefPubMedGoogle Scholar
  7. Good PD, Krikos AJ, Li SX et al (1997) Expression of small, therapeutic RNAs in human cell nuclei. Gene Ther 4:45–54CrossRefPubMedGoogle Scholar
  8. Elmen J, Lindow M, Schutz S et al (2008) LNA-mediated microRNA silencing in non-human primates. Nature 452:896–899CrossRefPubMedGoogle Scholar
  9. James W, al-Shamkhani A (1995) RNA enzymes as tools for gene ablation. Curr Opin Biotechnol 6:44–49CrossRefPubMedGoogle Scholar
  10. Krutzfeldt J, Rajewsky N, Braich R et al (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438:685–689CrossRefPubMedGoogle Scholar
  11. Lim LP, Glasner ME, Yekta S et al (2003) Vertebrate microRNA genes. Science 299:1540CrossRefPubMedGoogle Scholar
  12. Matteucci MD, Wagner RW (1996) In pursuit of antisense. Nature 384:20–22PubMedGoogle Scholar
  13. Mendoza-Maldonado R, Zentilin L, Giacca M (2001) Purging of chronic myelogenous leukemia cells by retrovirally expressed anti-bcr/abl ribozymes with specific celluar compartmentalization. Cancer Gene Ther 9:71–86CrossRefGoogle Scholar
  14. Mishra PK, Tyagi N, Kumar M, Tyagi SC (2009) MicroRNAs as a therapeutic target for cardiovascular disease. J Cell Mol Med 13:778–789CrossRefPubMedGoogle Scholar
  15. Paddison PJ, Caudy AA, Hannon GJ (2002) Stable suppression of gene expression by RNAi in mammalian cells. Proc Natl Acad Sci U S A 99:1443–1448CrossRefPubMedGoogle Scholar
  16. Prislei S, Buonomo SB, Michienzi A, Bozzoni I (1997) Use of adenoviral VAI small RNA as a carrier for cytoplasmic delivery of ribozymes. RNA 3:677–687PubMedGoogle Scholar
  17. Reynolds A, Leake D, Boese Q et al (2004) Rational siRNA design for RNA interference. Nat Biotechnol 22:326–330CrossRefPubMedGoogle Scholar
  18. Rossi JJ (2008) Expression strategies for short hairpin RNA interference triggers. Hum Gene Ther 19:313–317CrossRefPubMedGoogle Scholar
  19. Scherer LJ, Rossi JJ (2003) Approaches for the sequence-specific knockdown of mRNA. Nat Biotechnol 21:1457–1465CrossRefPubMedGoogle Scholar
  20. Seidman MM, Glazer PM (2003) The potential for gene repair via triple helix formation. J Clin Invest 112:487–494PubMedGoogle Scholar
  21. Soutschek J, Akinc A, Bramlage B et al (2004) Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432:173–178CrossRefPubMedGoogle Scholar
  22. Stein CA, Chen YC (1993) Antisense oligonucleotides as therapeutic agents: Is the bullet really magical? Science 261:1004–1012CrossRefPubMedGoogle Scholar
  23. Suarez Y, Sessa WC (2009) MicroRNAs as novel regulators of angiogenesis. Circ Res 104:442–454CrossRefPubMedGoogle Scholar
  24. Thompson JD, Macejak D, Couture L, Stinchcomb DT (1995) Ribozymes in gene therapy. Nat Med 1:277–278CrossRefPubMedGoogle Scholar
  25. Weng DE, Masci PA, Radka SF et al (2005) A phase I clinical trial of a ribozyme-based angiogenesis inhibitor targeting vascular endothelial growth factor receptor-1 for patients with refractory solid tumors. Mol Cancer Ther 4:948–955CrossRefPubMedGoogle Scholar
  26. Xia H, Mao Q, Paulson HL, Davidson BL (2002) siRNA-mediated gene silencing in vitro and in vivo. Nat Biotechnol 20:1006–1010CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2010

Authors and Affiliations

  • Mauro Giacca
    • 1
  1. 1.International Centre for Genetic Engineering and Biotechnology (ICGEB)TriesteItaly

Personalised recommendations