LNA longRNA GapmeR µðÀÚÀÎ Åø ¹Ù·Î°¡±â
Exiqon»çÀÇ Â÷¼¼´ë µðÀÚÀÎ ¾Ë°í¸®ÁòÀ¸·Î Á¦ÀÛµÈ antisense oligonucleotides¿Í RNaseH-activating ±â´ÉÀ» °¡Áø GapmeR´Â ¶Ù¾î³­ mRNA¿Í lncRNA ±â´É ¾ïÁ¦ ´É·Â°ú ³ôÀº ¼º°ø·üÀ» º¸ÀδÙ.

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LNA longRNA GapmeR´Â mRNA¿Í long non-coding RNA (lncRNA) ±â´É ºÐ¼®¿¡ »ç¿ëµÇ´Â antisense oligonucleotides (ASO)ÀÌ´Ù. GapmeR´Â ¾ç ¸»´Ü¿¡ LNA modified nucleotides (LNA blocks)¿Í ±× »çÀÌ DNA monomer·Î ÀÌ·ç¾îÁø DNA gap (central stretch)ÀÇ ±¸Á¶·Î µÇ¾îÀÖ´Ù (Figure 1). LNA Block ºÎÀ§´Â target¿¡ ´ëÇÑ affinity¸¦ ³ôÀ̰í nuclease¿¡ ÀÇÇÑ oligo ºÐÇØ ³»¼ºÀ» Áõ°¡½ÃŲ´Ù. DNA gap ºÎÀ§´Â target RNA¿Í °áÇսà RNaseH°¡ Àý´ÜÇÏ´Â ºÎÀ§·Î GapmeR´Â 14-16 nucleotides·Î fully phosphorothioated backboneÀ» Æ÷ÇÔÇϰí ÀÖ´Ù.

Figure1. Structure and function of the LNA longRNA GapmeRs. Gapmers contain a DNA part flanked by LNA (A). The LNA parts increase the affinity for the target and confers nuclease resistance (B). RNase H is activated by the DNA part of the ASO (C).

GapmeR: RNaseH Ȱ¼ºÀ» ÀÌ¿ëÇÏ¿© È¿°úÀûÀ¸·Î À¯ÀüÀÚ silencing À¯µµ
GapmeR antisense oligonucleotide (ASO)¿Í RNaseH Ȱ¼ºÀº È¿°úÀûÀ¸·Î À¯ÀüÀÚ ±â´ÉÀ» ¾ïÁ¦ÇÏ´Â ¹æ¹ýÀÌ´Ù. RNaseH´Â ¼¼Æ÷ÀÇ ÇÙ (nucleus)°ú ¼¼Æ÷Áú (cytoplasm)¿¡¼­ ¹ß°ßµÇ´Â ubiquitous enzymeÀÌ´Ù. Target mRNA ¶Ç´Â lncRNA¿Í antisense oligonucleotide GapmeR°¡ ¼­¿­ ƯÀÌÀûÀ¸·Î °áÇÕÇϸé RNaseH°¡ RNA-DNA heteroduplex¸¦ ÀνÄÇÏ¿© RNA¸¦ °¡¼öºÐÇØÇÑ´Ù. RNaseH¿¡ ÀÇÇØ ºÐÇØµÈ mRNA´Â ´Ü¹éÁú ¹ø¿ªÀÌ ÀúÇØµÇ¾î °á°úÀûÀ¸·Î target proteinÀÇ ¹ßÇöÀÌ ÀúÇØ(down regulation)µÈ´Ù (Figure 2).

Figure 2. Silencing of mRNA and long non-coding RNA using LNA™ longRNA GapmeRs.
LNA™ longRNA GapmeRs can bind to their target RNAs in both the nucleus and cytoplasm of the cell. The targeted molecules are then degraded in an RNase H-mediated process. Upon cleavage by RNase H, degraded mRNA will not be translated into their corresponding proteins which results in down-regulation of the protein.

Table1. Workflow for LNA™ longRNA GapmeRs. Exiqon's gapmers are available for all stages of an inhibition study:from the initial screening to large scale in vivo inhibtion.

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300600

LNA™ longRNA GapmeR, in vitro Standard, 5 nmol

300601-00

LNA™ longRNA GapmeR, in vitro Premium, ready to label, 5 nmol

300601-04

LNA™ longRNA GapmeR, in vitro Premium, 5¡¯ fluorescein label, 5 nmol

300601-08

LNA™ longRNA GapmeR, in vitro Premium, 3¡¯ fluorescein label, 5 nmol

300602-00

LNA™ longRNA GapmeR, in vivo Ready, ready to label, 5 nmol

300602-04

LNA™ longRNA GapmeR, in vivo Ready, 5¡¯ fluorescein label, 5 nmol

300602-08

LNA™ longRNA GapmeR, in vivo Ready, 3¡¯ fluorescein label, 5 nmol

300603-00

LNA™ longRNA GapmeR, in vivo Ready, ready to label, 20 nmol

300603-04

LNA™ longRNA GapmeR, in vivo Ready, 5¡¯ fluorescein label, 20 nmol

300603-08

LNA™ longRNA GapmeR, in vivo Ready, 3¡¯ fluorescein label, 20 nmol

500175

Custom LNATM longRNA GapmeR for in vivo use, modifications on demand, custom large scale (mg)