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Artificial mRNA and tRNA as Medicines

mrna trna protein

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#1 mag1

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Posted 28 December 2014 - 09:17 PM


Could anyone suggest why artificial mRMA or tRNA has not already been used as a medicine?

 

If artificial mRNA were introduced into cells then therapeutic proteins of any description could be manufactured. This approach might even be better than editing DNA as one would be able to switch protein expression whenever one chose. It is such a drag  

today to be limited by the proteins one was born with. It would be a very interesting world if your life experience (and protein production) were not under such strict constraint. mRNA could be regulated by ingested pharmaceuticals. 



#2 John Schloendorn

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Posted 28 December 2014 - 11:42 PM

RNA (and DNA) entities are very rarely approved as medicines, because one can't usually deliver sufficient quantities of these large molecules to enough cells in the tissues of an existing organism.  It's often a game of guessing in which tissues and diseases you can get away with minimal delivery efficiency.  Recent notable companies who did this well enough are Isis Pharmaceuticals and uniQure.  

 

If you could generally deliver enough construct, then there might be additional theoretical safety and efficacy questions like the ones you allude to.  But that's hypothetical.  The hard problem is large molecule delivery.

 

For protein production, we generally prefer DNA constructs over mRNA, because it's permanent, heritable and thus very easy and inexpensive.  If you need a switch (which you often don't), then there are DNA-based switches like the IPTG and lactose autoinduction systems in E.coli, and the tetracycline and steroid-inducible systems in mammalian cells.  And/or you could encode an RNA based switch in your DNA construct ("riboswitch").

 

There is a role for tRNA in protein expression, for purposes of rare codon supplementation.  But there too, I prefer to encode the necessary features in DNA, or in modern days you might as well do away with the problem by having your genes synthesized from scratch, which allows you to take full control of codon choices. 

 

 



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#3 mag1

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Posted 01 January 2015 - 10:14 PM

The big picture solution here seems so remarkably obvious:

Deliver artificial ribosomes to cells,

Produce the proteins of your choice.

 

Why has this not been made into a grand project?

Having the ability to control protein production would transform the world. 

 

The basic biology has been known for years, so it must be difficult.

However, with political commitment and efforts from the scientific community the success for such an undertaking at least seems plausible.



#4 mag1

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Posted 23 January 2015 - 05:18 PM

How much larger are proteins compared to the corresponding mRNA?

http://modernatx.com/

#5 Darryl

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Posted 23 January 2015 - 07:07 PM

Short interfering RNA is commonly used to knockdown genes in the laboratory, and there are quite a few siRNAs that have entered clinical trials.

 



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#6 mag1

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Posted 23 January 2015 - 10:20 PM

How effective a life enhancement strategy would polyploidy with regulation be?

For example, if a human were to be designed with 100 copies of each chromosome and each gene
were to have added some regulatory region (for example, an inducible repressor which could be inactivated by
some exotic chemical when needed), then whenever a mutation or telomere problem arose a brand new copy of
a gene could be turned on.

Is the problem with human genetics simply that there is not enough redundancy? Trees have much more genetic
material than we do and have achieved impressive feats of longevity.





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