Morpholino-mediated increase in soluble Flt-1 expression results in decreased ocular and tumor neovascularization
Methods of inhibiting lymphangiogenesis and/or angiogenesis in a subject are provided. In one aspect, for example, a method of inhibiting angiogenesis in a subject can include binding an antisense morpholino to an mRNA splicing site of VEGFR1 selected from exon13_intron13 junction, intron13_exon14 junction, or a combination thereof. In another aspect, the morpholino includes a member selected from VEGFR1_MOe13, VEGFR1_MOi13, or a combination thereof.
1. A method of inhibiting angiogenesis in a subject wherein the method comprises binding an antisense morpholino to a splicing site of VEGR1 mRNA in the subject wherein the splicing site is selected from the group consisting of exon13_intron13 junction, intron 13_exon14 junction, or a combination thereof such that the VEGFR1 mRNA is spliced into an sFlt-1 isoform, wherein the antisense morpholino is at least 75% identical to SEQ ID NO: 1 or is at least 75% identical to SEQ ID NO: 2.
2. The method of claim 1 , wherein the antisense morpholino is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, or a combination thereof.
3. The method of claim 1 wherein the antisense morpholino has a sequence that is at least 75% identical to SEQ ID NO: 1.
4. The method of claim 1 wherein the antisense morpholino has a sequence that is at least 95% identical to SEQ ID NO: 1.
5. The method of claim 1 wherein the antisense morpholino has the sequence of SEQ ID NO: 1.
6. The method of claim 1 wherein the antisense morpholino has a sequence that is at least 75% identical to SEQ ID NO: 2.
7. The method of claim 1 wherein the antisense morpholino has a sequence that is at least 95% identical to SEQ ID NO: 2.
8. The method of claim 1 wherein the antisense morpholino has the sequence of SEQ ID NO: 2.
9. A pharmaceutical composition for inhibiting angiogenesis in a subject, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and an antisense morpholino capable of binding to a splicing site of VEGR1 mRNA selected from the group consisting of exon13_intron13 junction, intron 13_exon14 junction, or a combination thereof, wherein the antisense morpholino is at least 75% identical to SEQ ID NO: 1 or is at least 75% identical to SEQ ID NO: 2.
10. The composition of claim 9 , wherein the morpholino includes a member selected from the group consisting of VEGFR1 —Moe 13 (SEQ ID NO: 1), VEGFR1 —MOi 13 (SEQ ID NO: 2), or a combination thereof.
11. The composition of claim 9 wherein the antisense morpholino is at least 75% identical to SEQ ID NO: 1.
12. The composition of claim 9 wherein the antisense morpholino is at least 95% identical to SEQ ID NO: 1.
13. The composition of claim 9 wherein the antisense morpholino has the sequence of SEQ ID NO: 1.
14. The composition of claim 9 wherein the antisense morpholino is at least 75% identical to SEQ ID NO: 2.
15. The composition of claim 9 wherein the antisense morpholino is at least 95% identical to SEQ ID NO: 2.
16. The composition of claim 9 wherein the antisense morpholino has the sequence of SEQ ID NO: 2.