RNAi Delivery

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Big E
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RNAi Delivery

The first human trials for the treatment of macular degeneration using RNAi are now underway. The use of RNAi may lead to novel treatments for many diseases, yet, it appears that RNAi delivery and specificity are the hurdles to overcome. Novartis is beginning to employ nanotechnology and magnets for delivery. At present what in vivo delivery methods are the best and in the future which methods do you believe will be the most efficient at delivering RNAi in vivo?

Big E
Big E's picture
Here is a recent review

Here is a recent review article on methods of delivery of RNAi
Curr Opin Chem Biol. 2004 Dec;8(6):570-9.
RNA interference and chemically modified small interfering RNAs.

Ambion and invitrogen also have resources on rnai delivery

Scot E. DOwd Ph.D.
Scot E. DOwd Ph.D.'s picture
Rather than citing articles

Rather than citing articles can we post actual answers. I think everyone is able to query Pubmed. not a bash DaJo just saw the question and would love to read answers or discussions regarding delivery methods in animals.

David E
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I have used PEI for in vitro

I have used PEI for in vitro transfection with great success. Recently, PEI has demonstrated its usefulness for in vivo delivery of rnai as well. PEI is less complicated than other methodologies and proficient for rnai delivery in vivo.

Scot E. DOwd Ph.D.
Scot E. DOwd Ph.D.'s picture
Can such a method "PEI" be

Can such a method "PEI" be used for delivery in animal or tissue based models? Is there a method for use in tissue or animal models or in target tissue in an animal model?

David E
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Yes, there are several

Yes, there are several studies demostrating the usefulness of PEI in transfecting DNA or RNA directly into animals. Mostly IP administration some further glycosylate the PEI.

Adolfo_Ferrando
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I confess my ignorance. What

I confess my ignorance. What is PEI?
Adolfo

David E
David E's picture
Adolfo_Ferrando wrote:I

Adolfo_Ferrando wrote:

I confess my ignorance. What is PEI?
Adolfo

Poly(ethylenimine)

Jason King
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Once the efficacy of the

Once the efficacy of the siRNAs has been tested in-vitro, the way to go must be in introduce the optimal sequence(s) into viral vectors such as AAV or Lentis and then go in-vivo for long term knock down.

Schiffelers
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Electroporation for local

Electroporation for local administration and shielded cationic polymers for systemic. Although cationic polymers like PEI form quite good nanoparticles with siRNA the resulting particle is strongly positively charged making it prone to binding to every cell (non-target and target cells). To increase specificity, shielding the charge may prevent this loss to non-target tissues (and may be improved by adding specific targeting ligands). I'm not so sure about the virus-approach. Safety, praparation and 'how to turn expression of if you no longer want it' seem obstancels to me.

bag2522
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If i am not wrong , PEI

If i am not wrong , PEI polymer does it not cause any significant toxicity , i think thats the reason why it has not been used widely.

Schiffelers
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Another reason indeed to

Another reason indeed to shield the PEI. The charge is though to be primarily responsible for toxicity as it induces aggregation with negatively charged serum proteins, which get stuck in small capillaries.

But even then, the non-biodegradability is still a problem I agree, but shileding with PEG can at least pervent all the acute effects.

Jason King
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PEI should allow short term

PEI should allow short term knockdown, but why would you want to do a transient knockdown in patients?

Nothing beats a virus for long-term expression, and AAV is less immunogenic/toxic than PEI.

Nature always makes the best nanoparticles.