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Blood Protein from Rice

Scientists genetically engineer rice to produce a safe, pure, and much-needed human plasma protein.

By | October 31, 2011

WIKIMEDIA COMMONS, HENNINGKLEVJER HOMEPAGE IMAGE: ROLF SUSSBRICH

The highly sought-after plasma protein, human serum albumin (HSA), can now be produced at high yield and purity in rice, according to a report published today (October 31) in Proceedings of the National Academy of Sciences. Using the rice-derived protein in place of its blood-derived counterpart will not only ease demand but also eliminate the risk of spreading diseases.

“The authors have demonstrated large-scale purification and functional equivalence to human HSA,” said Richard Twyman of Pharma-Planta, an EU consortium aimed at producing pharmaceutical proteins in plants, and the University of Warwick, UK, who was not involved in the study. “They have potentially developed a very good alternative to provide HSA in the clinic.”

HSA is used for a variety of clinical applications such as the treatment of blood loss, serious burns, and abdominal fluid retention caused by cirrhosis (scarring) of the liver. In addition, HSA has served as a vehicle for vaccine and drug delivery, and as a cell culture supplement in the production of vaccines and pharmaceuticals.

“There is a high demand for plasma HSA, but it is in really short supply,” explained lead researcher Daichang Yang of Wuhan University, China. Currently, the only supply of HSA is that extracted from human blood. Besides the limited availability of blood donors, “using plasma HSA also has a high risk for spreading diseases, such as AIDS and hepatitis,” Yang said. “We considered using a plant-based production to satisfy the market demand and reduce the risk.”

Yang and his colleagues are not the first to attempt genetically engineering human HSA production in other species. Yeast, bacteria, potatoes, and tobacco plants have all been tried, but each has met with feasibility issues. “The problem with microbial HSA has been that tiny traces of microbial contaminants… are either toxic or induce immune reactions in humans, which means they require extensive purification and this adds tremendously to the costs,” explained Twyman. HSA produced in potatoes or tobacco does not carry such contamination risks, but neither of these sources has provided sufficient yield to be cost-effective.

To bump up yield, Yang and his colleagues turned to rice. Specifically, they targeted the part of rice we eat, the endosperm inside the seed—a natural nutrient storage organ, and thus an excellent site for the accumulation and long-term stable storage of recombinant proteins. By driving expression of the HSA gene in the endosperm, the team managed to obtain 2.74 grams of pure HSA protein per kilogram of rice seed, more than 25 times the 0.1 grams of HSA collected from one kilogram of tobacco leaves.

In addition to obtaining a high yield, the rice-derived HSA shared the same molecular weight, crystal structure, molecular binding sites, and other biochemical characteristics as that of blood-derived HSA. These similarities translated to functional equivalence in tests for ligand binding, promotion of cell growth in culture, and the treatment of fluid retention in a rat model of liver cirrhosis.

The rice-derived HSA also displayed an equivalent immunogenicity to that of plasma HSA. That is, animals injected with either rice HSA or plasma HSA developed similar immune reactions.

“The chemical, biophysical and immunological characterization of the highly purified protein from rice… shows it to be identical in every respect to human serum albumin isolated from blood plasma,” said Diter von Wettstein of Washington State University, who was not involved in the study.

Despite these similarities, before rice HSA can be used in humans it will need to go through extensive clinical trials. Furthermore, to generate sufficient quantities of HSA to meet global demand—an estimated 500 tons a year—production will need to be scaled up to open-field farming, which will bring its own share of red tape. So, while the prospects for rice HSA are exciting, Twyman says, “we are not going to see blood-derived HSA replaced tomorrow.”

Y. He et al., “Large-scale production of functional human serum albumin from transgenic rice seeds,” Proceedings of the National Academy of Sciences, doi/10.1073/pnas.1109736108, 2011.

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Comments

Avatar of: Aggirl

Aggirl

Posts: 4

November 1, 2011

Wondering what is required to grow this rice- more fertilizers and pesticides? What about other nutrient requirements and how long for it to grow? I am hoping this does not turn into something like the Biofuels episode. 

Avatar of: Stuart Saunders

Stuart Saunders

Posts: 8

November 1, 2011

That will require nearly 20,000 tonnes of rice per year, to produce the 500 tonnes of HSA. Is the unused rice portion otherwise useful?

Avatar of: Stuart Saunders

Stuart Saunders

Posts: 8

November 1, 2011

Oops, 200,000 tonnes.

Avatar of: Ed Rybicki

Ed Rybicki

Posts: 82

November 1, 2011

The floodgates are opening, people...soon most proteins will be made this way!  And not before time.

Avatar of:

Posts: 0

November 1, 2011

Wondering what is required to grow this rice- more fertilizers and pesticides? What about other nutrient requirements and how long for it to grow? I am hoping this does not turn into something like the Biofuels episode. 

Avatar of:

Posts: 0

November 1, 2011

That will require nearly 20,000 tonnes of rice per year, to produce the 500 tonnes of HSA. Is the unused rice portion otherwise useful?

Avatar of:

Posts: 0

November 1, 2011

The floodgates are opening, people...soon most proteins will be made this way!  And not before time.

Avatar of:

Posts: 0

November 1, 2011

Oops, 200,000 tonnes.

Avatar of:

Posts: 0

November 1, 2011

Wondering what is required to grow this rice- more fertilizers and pesticides? What about other nutrient requirements and how long for it to grow? I am hoping this does not turn into something like the Biofuels episode. 

Avatar of:

Posts: 0

November 1, 2011

That will require nearly 20,000 tonnes of rice per year, to produce the 500 tonnes of HSA. Is the unused rice portion otherwise useful?

Avatar of:

Posts: 0

November 1, 2011

Oops, 200,000 tonnes.

Avatar of:

Posts: 0

November 1, 2011

The floodgates are opening, people...soon most proteins will be made this way!  And not before time.

Avatar of:

Posts: 0

November 2, 2011

Will it directly add HSA in human blood if taken in diet,or can be used only after isolation and crystalization

Avatar of:

Posts: 0

November 2, 2011

It is nearly impossible to absorb proteins in their native state; digestive fluids destroy the functional structure, then enzymes cut the protein into tiny pieces.
HSA is a very large protein, containing approx. 600 amino acids.  Rice HSA would be nothing more than a source of protein if ingested.
Insulin is even too large & complex to be absorbed orally.
The only protein-based drugs that get absorbed intact, and sufficiently to have clinical effect, are the tiniest peptide sequences, such as desmopressin (9 amino acids).  Even then, the oral dose is ~100 times higher than the parenteral dose, just to get the same effect.

Avatar of:

Posts: 0

November 2, 2011

where oh where is the author getting the 500 Tons a year figure!  really!!?

Avatar of:

Posts: 0

November 2, 2011

If breweries can ship "waste" barley to dairy/cattle farmers for feed, I would hope Big Pharma could do something similar.
As long as they don't have to use harsh chemicals for the purification process, they could probably use the "waste" for rice-based products such as "milk," breakfast cereals, animal feeds... anything that doesn't require an intact rice grain.
Selling the "waste" would also help to offset the production costs.

Avatar of:

Posts: 0

November 2, 2011

where oh where is the author getting the 500 Tons a year figure!  really!!?

Avatar of:

Posts: 0

November 2, 2011

Will it directly add HSA in human blood if taken in diet,or can be used only after isolation and crystalization

Avatar of:

Posts: 0

November 2, 2011

It is nearly impossible to absorb proteins in their native state; digestive fluids destroy the functional structure, then enzymes cut the protein into tiny pieces.
HSA is a very large protein, containing approx. 600 amino acids.  Rice HSA would be nothing more than a source of protein if ingested.
Insulin is even too large & complex to be absorbed orally.
The only protein-based drugs that get absorbed intact, and sufficiently to have clinical effect, are the tiniest peptide sequences, such as desmopressin (9 amino acids).  Even then, the oral dose is ~100 times higher than the parenteral dose, just to get the same effect.

Avatar of:

Posts: 0

November 2, 2011

If breweries can ship "waste" barley to dairy/cattle farmers for feed, I would hope Big Pharma could do something similar.
As long as they don't have to use harsh chemicals for the purification process, they could probably use the "waste" for rice-based products such as "milk," breakfast cereals, animal feeds... anything that doesn't require an intact rice grain.
Selling the "waste" would also help to offset the production costs.

Avatar of: mistersoft

mistersoft

Posts: 2

November 2, 2011

where oh where is the author getting the 500 Tons a year figure!  really!!?

Avatar of: Dr. Ichha Purak

Dr. Ichha Purak

Posts: 1457

November 2, 2011

Will it directly add HSA in human blood if taken in diet,or can be used only after isolation and crystalization

Avatar of: johndossantos

johndossantos

Posts: 8

November 2, 2011

It is nearly impossible to absorb proteins in their native state; digestive fluids destroy the functional structure, then enzymes cut the protein into tiny pieces.
HSA is a very large protein, containing approx. 600 amino acids.  Rice HSA would be nothing more than a source of protein if ingested.
Insulin is even too large & complex to be absorbed orally.
The only protein-based drugs that get absorbed intact, and sufficiently to have clinical effect, are the tiniest peptide sequences, such as desmopressin (9 amino acids).  Even then, the oral dose is ~100 times higher than the parenteral dose, just to get the same effect.

Avatar of: johndossantos

johndossantos

Posts: 8

November 2, 2011

If breweries can ship "waste" barley to dairy/cattle farmers for feed, I would hope Big Pharma could do something similar.
As long as they don't have to use harsh chemicals for the purification process, they could probably use the "waste" for rice-based products such as "milk," breakfast cereals, animal feeds... anything that doesn't require an intact rice grain.
Selling the "waste" would also help to offset the production costs.

Avatar of: Ed Rybicki

Ed Rybicki

Posts: 82

November 3, 2011

Huh??  "2.74 grams of pure HSA protein per kilogram of rice seed..." = 2.74 kg/tonne = 5 kg/2 tonnes = 5 tonnes/2000 tonnes.  You out a few zeros there, Stuart!!

And world rice per year = 678 million tonnes in 2009 (Wikipedia), so HSA production would need only 0.0003% of the total world crop...and the Philippines average yield is ~4 tonnes/hectare, so one would need only 500 hectares for the whole WORLD supply.

Avatar of: Ed Rybicki

Ed Rybicki

Posts: 82

November 3, 2011

Plant-made vaccines or even just orally-introduced vaccines also elicit good immune responses via uptake by M-cells and other routes in the gut.  Turns out repeating structures - like viruses - are what certain toll-like receptors like.  So larger proteins can most definitely have a clinical effect.

Avatar of: mohammed glal

mohammed glal

Posts: 1

November 3, 2011

Problems standing in the way of this procedure center mostly around the agriculture industry as the production of food for purposes other than feeding Earth’s 7 billion human inhabitants becomes a greater concern.

Avatar of:

Posts: 0

November 3, 2011

Plant-made vaccines or even just orally-introduced vaccines also elicit good immune responses via uptake by M-cells and other routes in the gut.  Turns out repeating structures - like viruses - are what certain toll-like receptors like.  So larger proteins can most definitely have a clinical effect.

Avatar of:

Posts: 0

November 3, 2011

Problems standing in the way of this procedure center mostly around the agriculture industry as the production of food for purposes other than feeding Earth’s 7 billion human inhabitants becomes a greater concern.

Avatar of:

Posts: 0

November 3, 2011

Huh??  "2.74 grams of pure HSA protein per kilogram of rice seed..." = 2.74 kg/tonne = 5 kg/2 tonnes = 5 tonnes/2000 tonnes.  You out a few zeros there, Stuart!!

And world rice per year = 678 million tonnes in 2009 (Wikipedia), so HSA production would need only 0.0003% of the total world crop...and the Philippines average yield is ~4 tonnes/hectare, so one would need only 500 hectares for the whole WORLD supply.

Avatar of:

Posts: 0

November 3, 2011

Huh??  "2.74 grams of pure HSA protein per kilogram of rice seed..." = 2.74 kg/tonne = 5 kg/2 tonnes = 5 tonnes/2000 tonnes.  You out a few zeros there, Stuart!!

And world rice per year = 678 million tonnes in 2009 (Wikipedia), so HSA production would need only 0.0003% of the total world crop...and the Philippines average yield is ~4 tonnes/hectare, so one would need only 500 hectares for the whole WORLD supply.

Avatar of:

Posts: 0

November 3, 2011

Problems standing in the way of this procedure center mostly around the agriculture industry as the production of food for purposes other than feeding Earth’s 7 billion human inhabitants becomes a greater concern.

Avatar of:

Posts: 0

November 3, 2011

Plant-made vaccines or even just orally-introduced vaccines also elicit good immune responses via uptake by M-cells and other routes in the gut.  Turns out repeating structures - like viruses - are what certain toll-like receptors like.  So larger proteins can most definitely have a clinical effect.

Avatar of:

Posts: 0

November 9, 2011

"to meet global demand—an estimated 500 tons a year"

Ce?

Avatar of:

Posts: 0

November 9, 2011

"to meet global demand—an estimated 500 tons a year"

Ce?

Avatar of: Stuart Saunders

Stuart Saunders

Posts: 8

November 9, 2011

"to meet global demand—an estimated 500 tons a year"

Ce?

Avatar of: D

D' Miracle Healer

Posts: 1457

November 16, 2011

Rice Is One Of The Main Ingredients Used
For D' Miracle Healer's Medications like:-

Muscle Builder :- Helps in the development and
strengthening of the torn, dystrophy related muscles and/or ligament.

 Sedia - Helps
to get rid of blood viruses and bacteria.

 Kidney
Cleanser :- helps in kidney
cleansing, breaking of stones, clearing of clog, detoxification and blood
cleansing.

 Liquid food:- Act as
a hard food replacement with full nutrients required by the body.
https://www.facebook.com/d.mir...  check our facebook out

Avatar of:

Posts: 0

November 16, 2011

Rice Is One Of The Main Ingredients Used
For D' Miracle Healer's Medications like:-

Muscle Builder :- Helps in the development and
strengthening of the torn, dystrophy related muscles and/or ligament.

 Sedia - Helps
to get rid of blood viruses and bacteria.

 Kidney
Cleanser :- helps in kidney
cleansing, breaking of stones, clearing of clog, detoxification and blood
cleansing.

 Liquid food:- Act as
a hard food replacement with full nutrients required by the body.
https://www.facebook.com/d.mir...  check our facebook out

Avatar of:

Posts: 0

November 16, 2011

Rice Is One Of The Main Ingredients Used
For D' Miracle Healer's Medications like:-

Muscle Builder :- Helps in the development and
strengthening of the torn, dystrophy related muscles and/or ligament.

 Sedia - Helps
to get rid of blood viruses and bacteria.

 Kidney
Cleanser :- helps in kidney
cleansing, breaking of stones, clearing of clog, detoxification and blood
cleansing.

 Liquid food:- Act as
a hard food replacement with full nutrients required by the body.
https://www.facebook.com/d.mir...  check our facebook out

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