Synthetic organisms are about to challenge what ’being’ and ‘alive’ really means


We need to begin a serious debate about whether artificially evolved humans are our future, and if we should put an end to these experiments before it is too late.

In 2016, Craig Venter and his team at Synthetic Genomics announced that they had created a lifeform called JCVI-syn3.0, whose genome consisted of only 473 genes.

This stripped-down organism was a significant breakthrough in the development of artificial life as it enabled us to understand more fully what individual genes do. (In the case of JCVI-syn3.0, most of them were used to create RNA and proteins, preserve genetic fidelity during reproduction and create the cell membrane.

The functions of about a third remain a mystery.)

Venter’s achievement followed an earlier breakthrough in 2014, when Floyd Romesberg at Romesberg Lab in California succeeded in creating xeno nucleic acid (XNA), a synthetic alternative to DNA, using amino acids not found among the naturally occurring four nucleotides: adenine, cytosine, guanine and thymine. 

And, most recently we have seen huge advances in the use of CRISPR, a gene-editing tool that allows substitution or injection of DNA sequences at chosen locations in a genome.

Read More: Why Bill Gates is Betting on this Synthetic Biology Start-Up

Together, these developments mean that in 2019 we will have to take seriously the possibility of our developing multicellular artificial life, and we will need to start thinking about the ethical and philosophical challenges such a possibility brings up.

In the near future we can reasonably anticipate that a large number of unnatural single-cell life forms will be created using artificially edited genomes to correct for genetic defects or to add new features to an organism’s phenotype.

It is already possible to design bacterial forms, for example, that can metabolise pollutants or produce particular substances.

We can also anticipate that new life forms may be created that have never existed in nature through the use of conventional and perhaps artificially arranged codons (nucleotide sequences that manage protein synthesis).

These are likely to make use of the conventional machinery of mitotic cell reproduction and of conventional ribosomes, creating proteins through RNA or XNA interpretation.

And there will be increasing pressures to continue this research. We may need to accelerate the evolution of terrestrial life forms, for example, including homo sapiens, so that they carry traits and capabilities needed for life in space or even on our own changing planet. 

All of this will bring up serious issues as to how we see ourselves – and behave – as a species.

While the creation of multicellular organisms that are capable of sexual reproduction is still a long way off, in 2019 we will need to begin a serious debate about whether artificially evolved humans are our future, and if we should put an end to these experiments before it is too late.

 Vint Cerf of ‘Wired’

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Arizona State University ~ ‘Living Computers’ from RNA for Nanotechnology


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Researchers from Arizona State University have demonstrated that living cells can be induced to carry out complex computations in the manner of tiny robots or computers.

It’s an example of engineers and biologists coming together to create an innovative solution to the performing of calculations. The implications are a potential game-changer for intelligent drug design and smart drug delivery. Other fields that could be affected include green energy production, low-cost diagnostic technologies and the development of futuristic nanomachines to be used in gene-editing. ASU xximage_1.png.pagespeed.ic.dPihifYIDEThe basis of the new technology is the natural interactions between nucleic acid; in this case the predictable and programmable RNA-RNA interactions. RNA is ribonucleic acid, an important molecule with long chains of nucleotides.
A nucleotide contains a nitrogenous base, a ribose sugar, and a phosphate. RNA is involved with the coding, decoding, regulation, and expression of genes. This builds on earlier work where DNA and RNA, the molecules of life, where demonstrated as being able to perform computer-like computations by Leonard Adleman (University of Southern California) in 1994 (“Molecular Computation of Solutions To Combinatorial Problems.”)
Atomic structure of the 50S Large Subunit of the Ribosome. Proteins are colored in blue and RNA in o...

Atomic structure of the 50S Large Subunit of the Ribosome. Proteins are colored in blue and RNA in orange. RNA is central to the synthesis of proteins. Wikipedia / Vossman
From this basis, lead researcher Professor Alex Green has used computer software to design RNA sequences that behave the way researchers want them to in a cell. This makes the design process a much faster.RNA Nano 3 RNAThe output is circuit designs, which look like conventional electronic circuits, but which self-assemble inside bacterial cells. This allows the cells to sense incoming messages and respond to them by producing a computational output. To test this out, the researchers worked with specialized circuits called logic gates. The tiny circuit switches were tripped when messages (RNA fragments) which attached themselves to their complementary RNA sequences in the cellular circuit. This activated the logic gate and produced an output. A series of more complex logic gates were then designed, to respond to multiple inputs. Here logic gates known as AND, OR and NOT were designed.
The video below explains more about these switches:

From this the scientists developed the first ribocomputing devices capable of four-input AND, six-input OR and a 12-input device able to carry out a complex combination of AND, OR and NOT logic known as disjunctive normal form expression.The great strength of the new method is with its ability to perform many operations at the same time. This capacity for parallel processing allows for faster and more sophisticated computation.The example, of meshing engineering and biology together, is part of an emerging field called synthetic biology, and it is one of the fastest growing areas of scientific research. In a sense, synthetic biology is a biology-based “toolkit”. According to the European research group ERBC the science deploys abstraction, standardization, and automated construction to change how we build biological systems and expand the range of possible products. One such example of what a highly accurate platform like this could do is with diagnosing viruses the Zika virus.The research has been published in the journalNature under the title “Complex cellular logic computation using ribocomputing devices.”

 

Researchers Develop Novel Technique for Separating Target Molecules from Mixed Solutions Using Magnetic Nanoparticles


Published on September 18, 2013 at 7:04 AM

201306047919620Separating target molecules in biological samples is a critical part of diagnosing and detecting diseases. Usually the target and probe molecules are mixed and then separated in batch processes that require multiple pipetting, tube washing and extraction steps that can affect accuracy.

 

This is an illustration showing a simple new technique that is capable of separating tiny amounts of the target molecules from mixed solutions. Credit: J.Wang/Brown

 

Now a team of researchers at Brown University has developed a simple new technique that is capable of separating tiny amounts of the target molecules from mixed solutions by single motion of magnet under a microchannel. Their technique may make pipettes and test tubes a thing of the past in some diagnostic applications and increase the accuracy and sensitivity of disease detection.

The new platform developed by Anubhav Tripathi and his team at Brown doesn’t rely on external pumps to mix samples or flow target molecules. Instead, their system is static and handy for researchers to use, according to Ms. Jingjing Wang, a graduate student pursuing her PhD. Bead-like magnetic particles are specifically modified by attaching short pieces of DNA to them that can capture target DNA molecules with specific sequences matching. Those are then separated for detection simply by pulling the magnetic beads along the channel. The process is simple, fast and specific.

This process has great applicability particularly for point-of-care platforms that are used to detect bacterial, viral infections and prion diseases by DNA, RNA or protein identification. Specific disease applications include testing for HIV and influenza, explained Wang.

“It can also be used to evaluate the expression of certain protein markers, such as troponin (an indicator of damage to the heart muscle) or any detection that requires binding and separation of known target biomolecules,” she added.

Optimizing the system and characterizing the chip for biological assays was the biggest challenge for the research team as it required that both engineering as well as biological factors be considered, however the team is already developing assays using this new platform. A new microchip based Simple Method of Amplifying RNA Targets (SMART) assay developed to detect influenza from patient samples is already showing high agreement with Polymerase Chain Reaction (PCR), which is considered the “gold standard” for influenza diagnosis. The team’s next challenge is developing assays using this technique to detect wild type and drug-resistant HIV in areas with limited resources such as Kenya and South Africa.

Source: http://www.aip.org

Novel nanoparticle to deliver powerful RNA interference drugs


201306047919620(Nanowerk News) Silencing genes that have malfunctioned  is an important approach for treating diseases such as cancer and heart disease.  One effective approach is to deliver drugs made from small molecules of  ribonucleic acid, or RNA, which are used to inhibit gene expression. The drugs,  in essence, mimic a natural process called RNA interference.
In a new paper appearing today online in the journal, ACS  Medicinal Chemistry Letters (“In Vivo Delivery of RNAi by Reducible Interfering  Nanoparticles (iNOPs)”), researchers at Sanford-Burnham Medical Research  Institute have developed nanoparticles that appear to solve a big challenge in  delivering the RNA molecules, called small interfering RNA, or siRNA, to the  cells where they are needed. By synthesizing a nanoparticle that releases its  siRNA cargo only after it enters targeted cells, Dr. Tariq M. Rana and  colleagues showed in mice that they could deliver drugs that silenced the genes  they wanted.
“Our study describes a strategy to reduce toxic effects of  nanoparticles, and deliver a cargo to its target,” said Dr. Rana, whose paper,  “In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs),” also  included contributions from researchers at the University of Massachusetts  Medical School and the University of California at San Diego. “We’ve found a way  to release the siRNA compounds, so it can be more effective where it’s needed,”  Dr. Rana said.
In their experiment, the team synthesized what they call  interfering nanoparticles, or iNOPs, made from repetitively branched molecules  of a small natural polymer called poly-L-lysine. The iNOPs were specially  designed with positively charged residues connected by disulfide bonds and these  iNOPS assemble into a complex with negatively charged siRNA molecules. It’s the  bonds that ensure that the siRNA molecules remain with the nanoparticle, named  iNOP-7DS. However, once inside targeted cells, a naturally occurring and  abundant antioxidant called glutathione breaks the bond, releasing the siRNA  molecules. In their experiment, Dr. Rana and colleagues showed in the lab that  iNOP-7DS is reducible – that is, the disulfide bonds holding the siRNA molecules  can be broken.
They next showed that iNOP-7DS can be delivered effectively  inside cultured murine liver cells, where the siRNA molecules silenced a gene  called ApoB. This gene has been notoriously difficult to regulate in liver cells  with small molecule drugs; high levels of the protein that ApoB encodes can lead  to plaques that cause vascular disease.
Dr. Rana’s lab further showed in tests that their nanoparticle  remained stable in serum, suggesting that it is not degraded in the bloodstream.  Finally, the researchers showed in tests with mice that their nanoparticle  iNOP-7DS can be delivered effectively to the liver, spleen, and lung; and it  suppressed the level of messenger RNA involved in the expression of the ApoB  gene. In their in vivo experiment, they found that extremely small doses of  siRNA were effective.
The next step, Dr. Rana said, is to increase the efficacy of  iNOP-7DS in other in vivo experiments. “We would like to target not only ApoB,  but cancer causing genes as well and in other tissues. That is the next goal.”  By marshaling the naturally occurring phenomenon of RNA interference, scientists  are developing new ways to silence errant gene expression involved in illnesses.  The nanoparticles developed by Dr. Rana and colleagues offer a potential new  strategy for delivering this powerful therapeutic approach.
Source: Sanford-Burnham Medical Research Institute 

Read more: http://www.nanowerk.com/news2/newsid=31244.php#ixzz2YdY2x07g