Biomod/2011/LMU/FolD'N'Assemble/Project: Difference between revisions

From OpenWetWare
Jump to navigationJump to search
No edit summary
No edit summary
Line 28: Line 28:
===The Project===
===The Project===


For our project we decided on designing a DNA based drug delivery vehicle.


DNA, as a building material, is very easy and safe to work with. So the idea to use it as a delivery vehicle came up naturally. When molecules are transported into a cell (endocytosis), they are absorbed by endosomes. The endosomes lower their pH value to 4-5. We want to use that process of pH change to open our container and release its payload.
===Abstract===
Molecular self-assembly enables the bottom-up construction of functional and biocompatible nanocarrier systems for the signal-responsive release of pharmaceuticals inside the cell. Eukaryotic cells selectively transport molecules from the extracellular matrix via endocytosis into the intracellular endosome, which contains an acidic interior with a pH-value of roughly 6. Aiming at an endocytotoic uptake, we designed a drug delivery container based on the DNA origami method that uses a decrease of the pH value of the surrounding media as a trigger for the opening mechanism of the container. Our DNA container consists of two identical half cylinders that form a closed homo-dimeric cylinder when connected by pH sensitive DNA duplexes. For each connecting duplex, one of the single strands contains four cytosine triplets that form the i-motif at low pH values. In our experiments, we were able to demonstrate the pH-sensitive separation of the two container halves.
 
===The idea===
Cells absorb molecules using a process called endocytosis. The cell membrane coats the molecule an forms a vesicle. This vesicle (endosome) is transported into the cell. During this process the pH value in the vesicle is lowered.
 
If we want to transport drugs into the cell, we can use this change in pH to trigger the release of the drugs.
 
<center>
; So we decided to design a drug delivery system containing
:a container build with DNA origami
:a opening mechanism based on pH change
</center>
 
===The container===
The container consists of two identical cylinders, which are connected by complementary DNA strands. The whole container is roughly 160 nm long and has a diameter of 20 nm.
 
 
 
===The opening mechanism===
One of two complementary strands includes a special DNA sequence, the i-motif. The


The container consists of two identical halves, that connect to form a closed cylinder. The connection is the only part sensitive to the pH change and can be adjusted to dissolve at a specific pH value, without modifying the core structures.


[[Image:dimerisation.gif]]
[[Image:dimerisation.gif]]

Revision as of 03:39, 31 October 2011

The Project

Abstract

Molecular self-assembly enables the bottom-up construction of functional and biocompatible nanocarrier systems for the signal-responsive release of pharmaceuticals inside the cell. Eukaryotic cells selectively transport molecules from the extracellular matrix via endocytosis into the intracellular endosome, which contains an acidic interior with a pH-value of roughly 6. Aiming at an endocytotoic uptake, we designed a drug delivery container based on the DNA origami method that uses a decrease of the pH value of the surrounding media as a trigger for the opening mechanism of the container. Our DNA container consists of two identical half cylinders that form a closed homo-dimeric cylinder when connected by pH sensitive DNA duplexes. For each connecting duplex, one of the single strands contains four cytosine triplets that form the i-motif at low pH values. In our experiments, we were able to demonstrate the pH-sensitive separation of the two container halves.

The idea

Cells absorb molecules using a process called endocytosis. The cell membrane coats the molecule an forms a vesicle. This vesicle (endosome) is transported into the cell. During this process the pH value in the vesicle is lowered.

If we want to transport drugs into the cell, we can use this change in pH to trigger the release of the drugs.

So we decided to design a drug delivery system containing
a container build with DNA origami
a opening mechanism based on pH change

The container

The container consists of two identical cylinders, which are connected by complementary DNA strands. The whole container is roughly 160 nm long and has a diameter of 20 nm.


The opening mechanism

One of two complementary strands includes a special DNA sequence, the i-motif. The