Oligonucleotides encapsulated in pH sensitive liposomes are efficient toward Friend retrovirus.
Retroviruses present multiple RNA targets for antisense oligonucleotides. An oligodesoxyribonucleotide (15 mer) complementary to the region of the initiation codon AUG of the env gene mRNA of Friend retrovirus was an inhibitor of the translation of Env protein in vitro. No effect was observed on cells infected with Friend retrovirus. We observed that these oligomers were rapidly degraded in cellular medium. After encapsulation into liposomes, they inhibited the spreading of the virus for chronic or de novo infection. We have compared the efficiency of two compositions of liposomes: pH sensitive and non pH sensitive formulations. Oligomers encapsulated in pH sensitive liposomes were more active that those encapsulated in non pH sensitive liposomes. pH sensitive liposomes could allow to avoid degradation of oligomers by lysosomes.
Ropert
C
C
URA 147 CNRS, U 140 INSERM, Institut Gustave Roussy, Villejuif, France.
Lavignon
M
M
Dubernet
C
C
Couvreur
P
P
Malvy
C
C
D001483:Base Sequence; D016373:DNA, Antisense / Q000378:metabolism; D016503:Drug Delivery Systems; D005069:Evaluation Studies as Topic; D005622:Friend murine leukemia virus / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007942:Leukemia, Experimental; D008081:Liposomes; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism
D016373:DNA, Antisense; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D014759:Viral Envelope Proteins