Liposomes containing oligonucleotides

Details Liposomes containing oligonucleotides Liposomes containing oligonucleotides

2000-01-13

2001-12-25

Wang, Andrew (Department: 1635)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

C435S006120, C435S091100, C435S455000, C536S023100, C536S024500

Reexamination Certificate

active

06333314

ABSTRACT:

FIELD OF THE INVENTION
This invention is related to use antisense of sequences of ≦40 bases for enhancing radiosensitivity of radiation-resistant tumors and to cationic liposomes which are particularly useful as carriers for antisense sequences.
BACKGROUND OF THE INVENTION
Radiation therapy is an important treatment modality of cancer. However, therapeutic management may be limited by the inherent relative resistance of some cancers to the cytotoxic effects of ionizing radiation. Recently, several lines of investigation have coalesced to demonstrate a link between certain oncogenes (ras, raf, cot, mos, myc), growth factors (PDGF, FGF) and the phenomenon of cellular resistance to ionizing radiation.
It was previously reported that expression of antisense c-raf-1 cDNA results in reduced expression (RNA) of c-raf-1 gene, a cause of delayed tumor growth in athymic mice and in enhanced radiation sensitivity of relatively radioresistant laryngeal squamous carcinoma cells, SQ-20B (Kasid et al., Science 243:1354-1356, 1989).
SUMMARY OF THE INVENTION
It is possible to radiosensitize tumor cells by administration of compositions containing the Human antisense c-raf-1 oligodeoxyribonucleotide (ODN/oligo) sequence:
5′-GTGCTCCATTGATGC-3′ (seq. ID No. 1) wherein only the end bases are phosphorylated is a preferred sequence. Antisense sequences of up to 40 bases which containing this sequence may be used in accord with the teachings of this disclosure. A composition of the 25-mer oligo:
5′-CCTGTAT
GTGCTCCATTGATGC
AGC-3′ (seq. ID No. 2) wherein the sequence is also effective. Compositions comprising cationic liposomes containing at least one non-toxic cationic lipid, phosphatidylcholine and cholesterol may be used as a carrier system.


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