Antisense oligonucleotides targeting folate receptor alpha, and the use thereof
a technology of antisense oligonucleotides and folate receptors, applied in the field of antisense oligonucleotides, can solve problems such as undesirable, and achieve the effects of suppressing the growth of cancerous cells and inhibiting the expression of fr
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Benefits of technology
Problems solved by technology
Method used
Image
Examples
example 1
[0074] Reduction of Newly Synthesized αhFR Protein Levels by αhFR Antisense Oligonucleotides.
[0075] Expression of αhFR is known to be elevated in cancer. In particular, increased αhFR expression is found in 90% of human epithelial ovarian malignancies and is associated with a poor disease prognosis. It is possible that over expression of αhFR confers a growth survival advantage in ovarian cancer cells, since folates are involved in numerous cellular processes, including DNA and RNA synthesis. Knocking out receptor function in αhFR-positive cells may therefore prove to be of clinical value in combating ovarian malignancies. Eight different antisense 21 mer oligonucleotides were designed to target the αhFR open reading frame (FIG. 2A) in an attempt to knock out αhFR expression in folate-deficient KB cells, which express significantly high levels of αhFR. FIG. 2B shows that KB cells incubated with 50 μM of AS-1, AS-2 or AS-6 reduced the levels of newly synthesized a αhFR by (up to app...
example 2
[0076] Decreased Viability of Cells Treated With a αhFR Antisense Oligonucleotides.
[0077] The effect of AS-6 on the viability of cultured KB cells was evaluated (FIG. 3). In a reproducible manner, KB cells incubated with 10 or 50 μM AS-6 showed a 20 and 60% decrease, respectively, in overall protein content, compared to the S-6 control. The decrease in cell viability upon AS-6 treatment correlates well with the decrease in newly synthesized αhFR expression, as determined in FIG. 2B. These observations suggest a requirement of αhFR expression for survival of KB cells.
example 3
[0078]αhFR-Targeted Ribozymes Efficiently Cleave αhFR mRNA Sequences.
[0079] Ribozymes are RNAs which are capable of catalyzing RNA cleavage reactions. The hammerhead ribozymes has been extensively studied and involves three putative helical systems: a highly conserved structure that is implicated in catalysis and two flanking regions that can be designed to target the cleavage of the mRNA of interest. Although ribozymes share the potential applications with antisense oligonucleotides, they have the added advantage of catalytic activity that theoretically can allow a single molecule to destroy one or more target RNA. As an alternative approach for knocking out αhFR function, two ribozymes were designed targeted to the 5′ region of the αhFR open reading frame (FIG. 4A). FIG. 4B demonstrates efficient cleavage of in vitro synthesized αhFR mRNA sequences by in vitro synthesized αhFR-targeted ribozymes. The correct size cleavage products for Rz 43 / 65 WT (236 and 846 bp) and Rz 187 / 210 W...
PUM
| Property | Measurement | Unit |
|---|---|---|
| volume | aaaaa | aaaaa |
| volume | aaaaa | aaaaa |
| pharmaceutical composition | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More