ABSTRACT
Antisense oligonucleotide (ASO), popularly known as oligo, is a single stranded deoxyribonucleotide/ribonucleotide sequence (<50 bp in length) that has the capability to hybridize with a target gene/mRNA through Watson-Crick base pairing, resulting in an arrested or reduced expression of that gene. The potential of ASO in therapeutics was rst identied by Zemencnik and Stephenson (Fattal and Bochot 2008) when they observed that oligonucleotide complementary to 3′ end of Rous sarcoma virus could block the viral replications in chicken broblast. The exquisite
12.3.1.7 Breast Cancer ................................................................... 319 12.3.1.8 Other Cancers .................................................................. 320
12.3.2 Therapeutic Approaches for Other Diseases .................................... 320 12.3.2.1 Diabetes Mellitus ............................................................. 320 12.3.2.2 Diabetic Retinopathy ....................................................... 321 12.3.2.3 Cytomegalovirus Retinitis-Associated Acquired
Immunodeciency Syndrome .......................................... 321 12.3.2.4 Human Papilloma Virus .................................................. 321 12.3.2.5 Viral Hemorrhagic Fever ................................................. 322 12.3.2.6 Hepatitis B Virus ............................................................. 322 12.3.2.7 Herpes Simplex Virus ...................................................... 322 12.3.2.8 Neurodegenerative Disorders ........................................... 322 12.3.2.9 Asthma ............................................................................. 325 12.3.2.10 Crohn’s Disease ................................................................ 325
12.4 Pharmacokinetics of Antisense Oligonucleotides ........................................ 325 12.4.1 Biodistribution of Antisense Oligonucleotides Depending
on Routes of Administration ............................................................. 325 12.4.1.1 Intravenous/Subcutaneous Administration ...................... 325 12.4.1.2 Intrathecal Administration ............................................... 327
12.5 Cellular Uptake of Antisense Oligonucleotides............................................ 327 12.6 Different Delivery Approaches Taken for Antisense Therapy ..................... 329
12.6.1 Lipid-Based Carrier Systems ............................................................ 330 12.6.1.1 Cationic Lipid .................................................................. 331 12.6.1.2 Neutral Lipid/Helper Lipid .............................................. 331 12.6.1.3 Anionic Lipid ................................................................... 331 12.6.1.4 PEG-Lipids ...................................................................... 331 12.6.1.5 Targeting Ligand .............................................................. 332 12.6.1.6 Lipid-Polymer Conjugate ................................................ 332
12.6.2 Techniques of Formulation ............................................................... 332 12.6.2.1 Direct Mixing .................................................................. 332 12.6.2.2 Detergent Dialysis ............................................................ 332 12.6.2.3 Ethanol Dialysis ............................................................... 333
12.7 Recent Findings ............................................................................................ 333 12.8 Conclusion .................................................................................................... 334 References .............................................................................................................. 335
specicity of ASO relies on the concept that a particular sequence of 17 bases in DNA occurs only once in the human genome (Martimprey et al. 2009). Since its advent, ASO has gained a lot of attention among researchers as smarter therapeutic alternatives against some deadly diseases such as cancer and other genetic disorders (Fattal and Bochot 2008).
