Intravitreal administration of antisense oligonucleotides: Potential of liposomal delivery

Antisense oligonucleotides are short synthetic fragments of genes that are able to inhibit gene expression after being internalized by cells. They can therefore be used as antiviral compounds particularly, for the treatment o f ocular viral infections (i.e. Herpes simplex virus or Cytomegalovirus, CM V). Antisense oligonucleotides are however poorly stable in biological flui ds and their intracellular penetration is limited. Although oligonucleotide s are now currently used in therapeutics for the treatment of CMV by intrav itreal injection (Vitravene(R)), their main drawbacks impose to repeat the number of administrations which can be very harmful and damaging. A system that is able to permit a protection of oligonucleotides against degradation and their slow delivery into the vitreous would be more favorable for impr oving patient compliance. The use of liposomes for intravitreal administrat ion can be very promising since these lipid vesicles are able to protect ol igonucleotides against degradation by nucleases and they allow to increase the retention time of many drugs in the vitreous. In this review, the poten tialities of liposomes far the intravitreal delivery of oligonucleotides wi ll be discussed. (C) 2000 Elsevier Science Ltd. All rights reserved.