Apr 11, 1995

Delivery of antisense oligodeoxyribonucleotides against the human epidermal growth factor receptor into cultured KB cells with liposomes conjugated to folate via polyethylene glycol

Proceedings of the National Academy of Sciences of the United States of America
S WangP S Low

Abstract

Antisense oligodeoxyribonucleotides targeted to the epidermal growth factor (EGF) receptor were encapsulated into liposomes linked to folate via a polyethylene glycol spacer (folate-PEG-liposomes) and efficiently delivered into cultured KB cells via folate receptor-mediated endocytosis. The oligonucleotides were a phosphodiester 15-mer antisense to the EGF receptor (EGFR) gene stop codon (AEGFR2), the same sequence with three phosphorothioate linkages at each terminus (AEGFR2S), a randomized 15-mer control of similar base composition to AEGFR2 (RC15), a 14-mer control derived from a symmetrized Escherichia coli lac operator (LACM), and the 5'-fluorescein-labeled homologs of several of the above. Cellular uptake of AEGFR2 encapsulated in folate-PEG-liposomes was nine times higher than AEGFR2 encapsulated in nontargeted liposomes and 16 times higher than unencapsulated AEGFR2. Treatment of KB cells with AEGFR2 in folate-PEG-liposomes resulted in growth inhibition and significant morphological changes. Curiously, AEGFR2 and AEGFR2S encapsulated in folate-PEG-liposomes exhibited virtually identical growth inhibitory effects, reducing KB cell proliferation by > 90% 48 hr after the cells were treated for 4 hr with 3 microM oligonucle...Continue Reading

  • References12
  • Citations122

Citations

Mentioned in this Paper

Monoclonal Antibodies
Drug Carriers
EGFR
Epidermal Growth Factor
Epidermal Growth Factor Receptor Activity
Uptake
Codon, Terminator
Fluorescein
Indirect Immunofluorescence
Gene Expression

About this Paper

Related Feeds

Antisense Oligonucleotide - Therapies For ALS

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
C P Leamon, P S Low
Journal of Controlled Release : Official Journal of the Controlled Release Society
J A Reddy, P S Low
Proceedings of the National Academy of Sciences of the United States of America
D M KranzE J Roy
© 2020 Meta ULC. All rights reserved