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Protein cannot pass cell membrane because it's a large molecule. Until now, is there any technique that can make protein pass through the cell membrane in vivo? I want to create a protein-drug that must be accessible DNA to reach it's site of reaction. How possible can i do it?

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Various protein transfection methods are available.

The simplest one is electroporation. By using electric pulses, transient pores can be formed, so that proteins outside can go the inside of membrane.

Several protein transfection reagents are commercially available. I think the mechanism is similar to lipofection of DNA.

http://www.clontech.com/US/Products/Transfection_and_Cell_Culture/Protein_Transfection/Protein_Transfection_Reagent https://www.neb.com/products/m2563-transpass-p-protein-transfection-reagent https://www.thermofisher.com/order/catalog/product/89850

Fusion with the transactivating transcription factor (TAT) protein transduction domain from the HIV TAT protein. This 11-amino acid sequence help proteins cross plasma membrane.

http://www.nature.com/mt/journal/v8/n1/full/mt2003155a.html


I am adding a couple of methods here.

Liposomes

Liposomes were designed to deliver drugs to places where the effects are wanted. Drugs are enclosed in liposome vesicles, but when reaching plasma membrane, liposomes could fusion with plasma membrane and release drugs inside of liposomes, although all liposomes are not designed to fuse cellular membrane. Lipo-fection of DNA is a bit different from this kind of liposomes because DNA is not necessarily enclosed in vesicles.

nanoparticles

This is relatively new. I do not have much knowledge about nanoparticles, but I know they are used to transfect DNA or RNA in vitro and in vivo. I do not know how popular nanoparticles for protein transfection are, but there are publications.

http://www.ncbi.nlm.nih.gov/pubmed/24859743

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    $\begingroup$ I don't think they let you electrocute patients these days, even just a little. $\endgroup$ – AMR Nov 21 '15 at 3:09
  • $\begingroup$ electroporation can perform in vivo , however it will make other free protein and free gene fragment outside pass through the cell membrane, what will happen? $\endgroup$ – DucFabulous Nov 21 '15 at 4:49
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    $\begingroup$ @AMR There are clinical studies using electroporation. For example: pancreatica.org/… , clinicaltrials.gov/ct2/show/NCT02079623 $\endgroup$ – 243 Nov 21 '15 at 6:19
  • $\begingroup$ @AMR electroporation is unlike electrocution. People have used in-vivo electroporation extensively in animal studies without any significant tissue damage and moreover as 243 said, clinical trials have been conducted using this technique. $\endgroup$ – WYSIWYG Nov 21 '15 at 6:42
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    $\begingroup$ @WYSIWYG The examples of electroporation use invasive measures to deliver the electrical charge to the tissue. It would not be practical if the OP is looking at systemic treatments or longer term, maintenance protocols, though the OP doesn't say, and you already are aware of my thoughts on this question. $\endgroup$ – AMR Nov 21 '15 at 20:52

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