Difference between revisions of "Part:BBa K3335006"

 
Line 1: Line 1:
 +
__NOTOC__
 +
<partinfo>BBa_K3335000 short</partinfo>
  
 +
Lung cancer is the major cause of cancer-related deaths globally. Mutant KRAS is a feature of 15%–50% of lung cancer cases[1]. Unfortunately, although much effort has been spent on searching for small molecule inhibitors of KRAS, KRAS gene has proven extraordinarily difficult to target by current pharmacological agents.
 +
 +
This year we developed an alternative strategy to silence the so-called untargetable and undruggable KRAS gene by employing exosome-mediated siRNA delivery.At the same time, we used iRGDLamp2b to achieve exosome targeting.
 +
 +
Particularly, we reprogrammed cells to simultaneously express KRAS siRNA and Lamp2b. Lamp2b is an exosomal membrane protein, in fusion with a tumor-penetrating internalizing RGD (iRGD) peptide (CRGDKGPDC), and then produce the tumor-targeting exosomes as KRAS siRNA delivery system.[1]
 +
 +
Tumor cells escape macrophage phagocytosis by overexpressing CD47.Therefore, we combined the fusion expression of iRGD and Lamp2b to characterize the exosome targeting.At the same time, siRNA targeting CD47 was produced, and mRNA expression was targeted to be reduced.This allows macrophages to avoid the effects of CD47 and attack tumor cells.
 +
 +
Tumor cells evade immune system surveillance by overexpressing PD-L1.Therefore, we combined the fusion expression of iRGD and Lamp2b to characterize the exosome targeting.At the same time, siRNA targeting PD-L1 is produced to reduce mRNA expression.This allows the immune system to avoid the effects of PD-L1 and attack tumor cells.
 +
 +
Therefore, siRNA targeting KRAS, PD-L1 and CD47 were simultaneously expressed to inhibit the proliferation of tumor cells while avoiding tumor escape, so as to kill tumor cells with its own immune system.
 +
 +
[1]]Yu Zhou et al.,Tumor-specific delivery of KRAS siRNA with iRGD-exosomes efficiently inhibits tumor growth. ExRNA,2019.
 +
 +
<!-- Add more about the biology of this part here -->
 +
===Usage and Biology===
 +
 +
<!-- -->
 +
<span class='h3bb'>Sequence and Features</span>
 +
<partinfo>BBa_K3335006 SequenceAndFeatures</partinfo>
 +
 +
 +
<!-- Uncomment this to enable Functional Parameter display -->
 +
===Functional Parameters===
 +
<partinfo>BBa_K3335006 parameters</partinfo>
 +
hello world
 +
<!-- -->

Revision as of 08:51, 22 October 2020

We use KIBRA to control exosome secretion

Lung cancer is the major cause of cancer-related deaths globally. Mutant KRAS is a feature of 15%–50% of lung cancer cases[1]. Unfortunately, although much effort has been spent on searching for small molecule inhibitors of KRAS, KRAS gene has proven extraordinarily difficult to target by current pharmacological agents.

This year we developed an alternative strategy to silence the so-called untargetable and undruggable KRAS gene by employing exosome-mediated siRNA delivery.At the same time, we used iRGDLamp2b to achieve exosome targeting.

Particularly, we reprogrammed cells to simultaneously express KRAS siRNA and Lamp2b. Lamp2b is an exosomal membrane protein, in fusion with a tumor-penetrating internalizing RGD (iRGD) peptide (CRGDKGPDC), and then produce the tumor-targeting exosomes as KRAS siRNA delivery system.[1]

Tumor cells escape macrophage phagocytosis by overexpressing CD47.Therefore, we combined the fusion expression of iRGD and Lamp2b to characterize the exosome targeting.At the same time, siRNA targeting CD47 was produced, and mRNA expression was targeted to be reduced.This allows macrophages to avoid the effects of CD47 and attack tumor cells.

Tumor cells evade immune system surveillance by overexpressing PD-L1.Therefore, we combined the fusion expression of iRGD and Lamp2b to characterize the exosome targeting.At the same time, siRNA targeting PD-L1 is produced to reduce mRNA expression.This allows the immune system to avoid the effects of PD-L1 and attack tumor cells.

Therefore, siRNA targeting KRAS, PD-L1 and CD47 were simultaneously expressed to inhibit the proliferation of tumor cells while avoiding tumor escape, so as to kill tumor cells with its own immune system.

[1]]Yu Zhou et al.,Tumor-specific delivery of KRAS siRNA with iRGD-exosomes efficiently inhibits tumor growth. ExRNA,2019.

Usage and Biology

Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    INCOMPATIBLE WITH RFC[21]
    Illegal BamHI site found at 1534
    Illegal BamHI site found at 1716
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    INCOMPATIBLE WITH RFC[25]
    Illegal NgoMIV site found at 1277
  • 1000
    COMPATIBLE WITH RFC[1000]


Functional Parameters

hello world