Nanocarriers of Antisense Oligonucleotides in Diabetes

Antisense oligonucleotides are short strands of deoxyribonucleotides that are complementary to specifi c encoding mRNA sequences and can block gene expression. Their potential use as therapeutic and gene validation tools has elicited great interest. However, poor intracellular delivery into several tissues in living animals currently limits the range of in vivo applications of antisense oligonucleotides. Innovative solutions to this problem are coming from nanomedicine, a discipline recently born from the marriage of nanotechnology and medicine. Through the use of nanotechnology-derived composites (nanocarriers), nanomedicine helps traditional drugs to avoid the body’s defenses that the drug encounters following its systemic administration. In this chapter we will describe diabetes-relevant applications of nanocarriers as La Jolla Institute for Allergy & Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA. E-mail: [email protected] E-mail: [email protected] Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA; E-mail: [email protected] *Corresponding author List of abbreviations after the text. Nanocarriers of Antisense Oligonucleotides in Diabetes 65 delivery systems for antisense oligonucleotides. We divided the chapter in two sections. In the fi rst section we will 1) describe the modes of action of antisense oligonucleotides and the chemical modifi cations that have been developed to ameliorate resistance to nucleases, enhance affi nity and potency, and reduce toxicity; 2) the biological barriers encountered by the antisense oligonucleotides following their systemic administration; 3) the arsenal of solutions that nanomedicine can offer to enable the safe delivery of antisense oligonucleotides to the target site. In the second section, we will review the antisense oligonucleotides and delivery systems that have been developed as novel therapeutic weapons against diabetes. This includes research from our laboratory focusing on achieving targeted delivery of antisense oligonucleotides into T cells for therapy of Type 1 Diabetes.