DNA and metal particles/quantum dots
…the Pfizer BioNTech COVID-19 vaccine, which uses iron nanoparticles to transport RNA molecules into the human body…
https://www.g2.com/articles/nanobots
Smart vaccination
Smart vaccination is an intelligent nanobot technology that strengthens the human immune system. A great example is the Pfizer BioNTech COVID-19 vaccine, which uses iron nanoparticles to transport RNA molecules into the human body.
Challenges of nanobots
Medical companies want to adapt nanobots into their pharmaceutical process to design better cures. However, it isn’t as flowery as it seems. Blending complex algorithmic expressions with medical science is a tricky affair. But some high-level challenges stand in the way of a nano-powered future.
- Learning about potential applications: Nanotechnology requires studying materials to their tiniest detail and designing microscopic systems to run more extensive processes. While this strategy can optimize business outcomes much faster, manufacturing might be challenging.
- Destruction: Nanobots can create ballistic machinery or emplacements, destroying ecosystems. Nanotechnology can give way to thousands and thousands of acres of nuclear annihilation and even end humankind. For this reason, it’s imperative to consider all the use cases of nanotechnology before using it.
- Self-replication: Using artificial nanobots as a virus remedy can backfire in case a new variant develops. Nanobots must be produced, programmed, and designed with the correct expertise to fight against viruses. An absence of either might result in the uncontrollable self-replication of nanobots, resulting in a bigger problem than the virus itself.
- DNA hacking: Nanobots can intelligently trick the human body into producing unwanted immunity cells through DNA hacking. Collision of the nanoparticles with existing cell tissues can result in excessive internal injuries or bleeding, which may go unnoticed.
- Economic slowdown: The advent of nanotechnology would make computers efficient enough to work independently. Nanosystems that can process and deliver critical messages to the target would wipe out the need for the human workforce. The absence of specialized staff could result in global unemployment and slow the economic wheel.
- Robotic apocalypse: Nanobots are a precursor to a frightening robotic apocalypse. Malfunctioning during nanobot production can pull out dangerous cards that can activate a mechanical action. As nanobots can design improvements to themselves a trillion times in the presence of energy, leaving them unattended could wreak havoc.
https://patents.justia.com/patent/10420842
SUMMARY OF INVENTION
In this invention, we describe an improved nucleic acid origami platform providing functional, stable, safe, non-immunogenic, and remote controllable therapeutic nano-devices. The platform also provide the means to provide a cargo in a ligand concentration dependent manner, control the activity of the devices by closing them at predetermined conditions, separately control multiple types of cargo, extend the shelf life of molecules such as drugs, vaccines, proteins, growth factors, cytokines, RNA molecules etc., and a tunable system to prevent drug tachyphylaxis by suppressing the endocytosis of drug-bound receptors from the cell surface.
The platform is based on methods for modifying DNA origami devices by the addition of small molecule chemicals, peptides or large proteins, additional nucleic acid molecules, inorganic quantum dots, nanocrystals or nanoparticles, liposomes, polysaccharides, polymers, carbon nanotubes, and additional materials.
The methods can also include enzymatic or non-enzymatic modification of the composition and structure of the DNA from which the device is made, such as methylation, acetylation, hydroxylation, fixation by chemical means, coating, etc. Finally, the platform can be achieved by designing the DNA origami device to be made of DNA that does not include certain motifs such as CpG, AT-rich regions etc.
… or the nano-antenna of (c), upon receipt of said electromagnetic field, undergoes inductive coupling and subsequent heating thereby displacing the latch domain from the oligonucleotide of (c); and (iii) the aptamer domain of (a) or the oligonucleotide of (b) or (c), and the latch domain, when hybridized or bound to one another, hold the device in a closed configuration…
It has also been found in accordance with the present invention that the device as defined herein may be controlled from afar by attaching a metal nano-antenna capable of, upon receipt of said electromagnetic field, undergoing inductive coupling and subsequent heating thereby causing the device to undergo a conformational change from a closed to an open configuration…
https://afbiu.org/news/dna-robots
Pfizer and Bar-Ilan Prof. Bachelet to Collaborate on DNA Robots that Deliver Medical Proteins to Designated Tissue
Overcoming a Problem in Drug Design
By agreeing to support this technology, Pfizer has expressed confidence in Prof. Bachelet’s approach that shows great promise in helping overcome a major problem in drug design — the fact that doctors have almost no control where or when a drug will be active once it is administered.
Prof. Bachelet’s system opens up new possibilities for bio-embedded computers that can work as a coordinated team, responding to cellular signals, making a drug available or unavailable at will, and controlling drug interactions.
Potential to Target Cancer Cells
In explaining how to make a nanometric robot, Bachelet says, “We first of all create a selected DNA sequence, and then fold it by using a process called DNA origami. With this method, a person can give a command to a computer, which folds the DNA molecule as needed.”
According to Bachelet, this method has the potential to target cancer cells. These types of cells can be targeted as a result of using the DNA sequence to make a form of a clam that contains an anti-cancer drug. He adds, “…the clam can be designed to change its shape and release the drug only when it meets a cancer cell or the right tissue.”
A Returning Scientist, Prof. Bachelet came to BIU from the Massachusetts Institute of Technology (MIT) several years ago. He is among the 50 Returning Scientists who were brought back to Israel by BIU, thanks in part to funding provided by supporters of the American Friends of Bar-Ilan University.
https://www.nextbigfuture.com/2020/10/self-replicating-anti-viral-molecular-machines.html
Augmanity, a research company based in Rehovot, Israel, has synthesized molecular machines, made from nucleic acids, which are capable of digesting viral RNA and utilizing it to assemble additional copies of itself inside living cells.(www.biorxiv.org/content/10.1101/2020.08.12.248997v1)
The machine’s body plan combines several parts that build upon the target RNA, assembling an immobile, DNA:RNA 4-way junction, which contains a single gene encoding a hammerhead ribozyme (HHR). Full assembly of the machine’s body from its parts enables the subsequent elongation of the gene and transcription of HHR molecules, followed by HHR-mediated digestion of the target molecule. This digestion converts the target to a building block suitable for participation in the assembly of more copies of the machine, mimicking biological heterotrophy.
Above – Images of the prototype automaton attached to DNA rectangles.
The work was led by Ido Bachelet.
In 2014, Ido had developed nanobots that could open and close based on molecular sensing. This was going to be the basis for nano-surgery. They had made billions of the devices and would inject them into patients.
The company that made the nanobots was bought by Pfizer.
There has been no reports on the progress toward nanosurgery from Pfizer.
Now, Ido Bachelet appears to have left Pfizer and is working on more advanced nanorobots based upon DNA and RNA.
Augmanity researchers describe the general design of a prototypical machine, characterize its activity cycle and kinetics, and show that it can be efficiently and safely delivered into live cells. As a proof of principle, we constructed a machine that targets the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) GP64 gene, and show that it effectively suppresses viral propagation in a cell population, exhibiting predator/prey-like dynamics with the infecting virus. In addition, the machine significantly reduced viral infection, stress signaling, and innate immune activation inside virus-infected animals. This preliminary design could control the behavior of antisense therapies for a range of applications, particularly against dynamic targets such as viruses and cancer.
The discovery and synthesis of the immobile DNA junction by Seeman, nearly 4 decades ago, emerged as a cornerstone of DNA nanotechnology, an expanding field with unique technological potential. The immobile junction enabled, for the first time, programming and control of the spatial positioning of matter at a single DNA base resolution, or approximately 3.5 angstroms. (https://www.biorxiv.org/content/10.1101/2020.08.12.248997v1.full.pdf)
In this work, a preliminary working prototype of such a system is reported. They describe a machine, or automaton, assembled from DNA and RNA, which incorporates structural and functional principles of DNA nanotechnology.
The automaton is designed as an immobile, DNA:RNA 4-way junction assembled from 3 parts, and contains a single gene which encodes a hammerhead ribozyme (HHR). Full assembly of the automaton’s body from its parts enables the subsequent transcription of HHR molecules and HHR-mediated digestion of the target molecule. This digestion renders the target suitable for participation in the assembly of more copies of the automaton, essentially mimicking biological heterotrophy. The starting material for self-replication, and for the subsequent “lifecycle” of the automaton, is a small seed population of fully-assembled machines, and a non-limiting amount of the separate DNA parts required for the assembly of new copies of the machine.
The automaton they describe here was inspired by pathogenic viruses and viroids, and is designed to be delivered into and operate inside living, virus-infected cells.
Inside the cells, the automaton’s goal is to counter viral infection by utilizing viral RNA as “food”.
The design reported here is modular, and can be adapted rapidly to counter new targets, for example viruses once their genome has been sequenced.
In addition, it could lead to new types of biologically-inspired, programmable agents for a range of therapeutic applications. Interestingly, this machine highlights complex anatomy and a hypothetical, rudimentary mechanism for predation, plausible features of molecular life forms from the RNA world.
DNA origami folding.
Previously-described DNA rectangles8 were re-designed using caDNAno33 to include 6 edge staples comprising the automaton S strand on its 3’ to enable rectangle-based assembly.
SOURCES – Biorxiv – An antiviral self-replicating molecular heterotroph
Written by Brian Wang, Nextbigfuture.com
http://nextbigfuture.com/2014/12/ido-bachelet-announces-2015-human-trial.html
One Trillion 50 nanometer nanobots in a syringe will be injected into people to perform cellular surgery.
The tiny molecular computers of the DNA nanobots can provide molecular selective control for powerful medicines that were already developed.
Using DNA origami and molecular programming, they are reality. These nanobots can seek and kill cancer cells, mimic social insect behaviors, carry out logical operators like a computer in a living animal, and they can be controlled from an Xbox. Ido Bachelet from the bio-design lab at Bar Ilan University explains this technology and how it will change medicine in the near future.
DNA is a natural substrate for computing and has been used to implement a diverse set of mathematical problems, logic circuits and robotics. The molecule also interfaces naturally with living systems, and different forms of DNA-based biocomputing have already been demonstrated. Here, we show that DNA origami can be used to fabricate nanoscale robots that are capable of dynamically interacting with each other in a living animal. The interactions generate logical outputs, which are relayed to switch molecular payloads on or off. As a proof of principle, we use the system to create architectures that emulate various logic gates (AND, OR, XOR, NAND, NOT, CNOT and a half adder). Following an ex vivo prototyping phase, we successfully used the DNA origami robots in living cockroaches (Blaberus discoidalis) to control a molecule that targets their cells.
https://www.biorxiv.org/content/10.1101/2020.08.12.248997v1
Abstract We report the synthesis of a molecular machine, fabricated from nucleic acids, which is capable of digesting viral RNA and utilizing it to assemble additional copies of itself inside living cells.
The starting material for self-replication, and for the subsequent “lifecycle” of the automaton, is a small seed population of fully-assembled machines, and a non-limiting amount of the separate DNA parts required for the assembly of new copies of the machine.
The design reported here is modular, and can be adapted rapidly to counter new targets, for example viruses once their genome has been sequenced.
In addition, it could lead to new types of biologically-inspired, programmable agents for a range of therapeutic applications. Interestingly, this machine highlights complex anatomy and a hypothetical, rudimentary mechanism for predation, plausible features of molecular life forms from the RNA world.
DNA and RNA nanostructures have been stably generated and studied in live cells64,65, and recent works have reported the successful delivery of DNA nanostructures into cells66,67 as well as packing DNA nanostructures in liposomes68,69, which improves their in-vivo stability.
In this regard, the current COVID-19 crisis highlights the important of these, traditionally overlooked, advantages of nucleic acid therapeutics.
Animal studies. Adult B. discoidalis of both sexes were purchased from two independent farms, Yaldei Ha-teva or Beit Haiut (Israel), and housed at room temperature and humidity in large plastic containers. Insects were supplied with dry pet food, fresh fruit, and water ad libitum. Egg cartons were used as light shelters. Maximum number of insects per cage was limited to 12….
https://www.biorxiv.org/content/10.1101/448761v2.full.pdf
Nanoscale robots exhibiting quorum sensing
The autoinducer release mechanism can be potentially adapted to any environment. For example, one could exploit the inherent instability of RNA for the gradual release of signal from the robots.
Alternatively, a UV-cleavable tether would release the signal only upon exposure of the robots to sunlight or another direct source of UV radiation.
In this work we implement, for the first time, collective behavior in molecular robots using a bio-inspired mechanism. The design presented here bears many similarities to bacterial QS, while carrying additional features such as the ability to be activated in response to chosen stimuli. Our work also provides a platform for the engineering of more elaborate communication schemes utilizing several sub-populations differing in autoinducer type and response thresholds, with desirable features as control systems for therapeutics and manufacturing.
https://web.archive.org/web/20181220045251/https://cordis.europa.eu/result/rcn/194933_en.pdf
https://www.biorxiv.org/content/biorxiv/early/2018/10/16/444851.full.pdf Digital therapeutics for distributed response to global pandemics
When studied from the angle of its worst-case scenario, surviving a highly infectious pandemic depends on a competition between the infectious pathogen and the therapeutic technology, each racing to reach the majority of the population first. This competition confronts us with several challenges: (i) the inevitable response time 𝑡R required for us to instigate a mitigation plan places the pathogen at a potentially significant spreading advantage; (ii) while the pathogen reproduces as it spreads1–3, a therapy must be manufactured and shipped from one or few sources, whose production and distribution capacity may be limited4–12; (iii) the dissemination of antibiotics or vaccines can be hindered by various external factors, such as geopolitical and socio-economical constraints13–16, which have little effect on the propagation of bacteria and viruses. But even if such factors are eliminated, e.g., assuming that an effective cure already exists, stockpiled in sufficient quantities and benefits from worldwide cooperation in its distribution, it would still have to outrun the pathogen, competing along the same routes of dissemination as the epidemic, i.e. the international transportation networks 17–23.
For a rapidly progressing epidemic, such competition may fail, having detrimental consequences in terms of human life.
It seems, therefore, that the only viable strategy is to severely intervene in international mobility, quarantining airports, restricting travel and effectively eliminating the routes supporting the viral spread 24–26, reserving them strictly for the distribution of the therapeutic agent.
Such major interventions, however, may result in a significant economic burden and major political stress, indeed – a lesser of two evils – but still a potentially hurtful toll on global stability.
Hence, we offer to break this gridlock by focusing on therapies that can spread via alternative, intrinsically more efficient, routes compared to those of physical transport. Such alternative is achievable if the therapeutic agent can be converted into digital information, handled and distributed as data, then locally printed, i.e. synthesized, at its designated destination (Box I). Indeed, the Internet provides infrastructure to distribute data extremely efficiently, outperforming any distribution network that mobilizes physical commodities. Hence, using this strategy, a digitizable therapeutic agent will compete within time-scales that are orders of magnitude shorter than those characterizing even the most virulent epidemics, benefiting from the effectively immediate transmission of data vs. the restricted physical medium on which pathogens propagate27.
polymer sequences, preferably short, of nucleic acids or peptides, which can be disseminated digitally
If we indeed develop the technology to mass-print short DNA strands, it is likely that highly populated nodes, will also have an increased capacity to synthesize the drugs, e.g., by scaling the number of printers with population size. Therefore, while typically 𝐶𝑆 P ≪ 1, confronting a single node vs. the global demand, 𝑐𝑛 D is likely of order unity for most 𝑛. Moreover, in real scenarios, nodes with 𝑐𝑛 D > 1 can aid less capable nodes by small scale per demand physical distribution – a practical strategy to further improve dissemination efficiency, that was not included in our current theoretical framework. Finally, in case of a novel pathogen, the discovery of a therapeutic aptamer is often significantly faster43 than that of molecular drugs (Box I), potentially reducing our response time 𝑡R, which as our analysis indicates, plays a crucial role in the mitigation efficiency.
Pfizer and BioNTech’s embrace of novel mRNA science played a pivotal role in achieving a record-breaking COVID-19 vaccine rollout. But a lesser-known part of this success story is Pfizer’s rapid adoption of new digital technologies to ensure the vaccine reached patients as safely and quickly as possible.
https://cdn.pfizer.com/pfizercom/partnering/recent_partnership/Pfizer-Bar_Ilan.pdf
https://dash.harvard.edu/bitstream/handle/1/13454727/4012984.pdf?sequence=1&isAllowed=y Universal computing by DNA origami robots in a living animal
https://www.pfizer.com/print/pdf/node/555751
Pivotal moments
COVID-19 pandemic: The pandemic was a game-changer in terms of how States approach economic and social rights as well as protect those most vulnerable from disease. For the UN Human Rights, the pandemic meant reinvigorating our work relating to social protection, as well as adjusting to new ways of (virtual) work and expanding the monitoring of human rights, Bachelet said.
Many existing human rights issues facing the world surfaced and required swift action, including deepening poverty, rising inequalities, lack of access to healthcare, vaccine and treatment, discrimination, and violence against women. This meant that her Office had to quickly provide solutions to these challenges.
UN Human Rights was able to, in a time of crisis and isolation, provide effective and practical guidance to Member States and civil society to identify human rights trends, risks, the impact of national responses, and how to handle the crises with a human rights approach.
Despite the benefits of connecting virtually, this meant the High Commissioner could not travel as much as we would have desired to accompany different actors on the ground in their human rights journeys.
The right to a healthy environment: Bachelet said she is most proud of her Office’s support and strong backing of the recognition of the human right to a clean, healthy and sustainable environment.
“The recognition of the human right to a clean, healthy and sustainable environment by the UN General Assembly last month marked the culmination of many years of advocacy by civil society. This is also an issue I personally have been working towards for many years and in different capacities, including as a Stateswoman,” she said.
She encouraged States to step up their obligation to fully implement the right to a healthy environment.
“The extreme weather events of the past few months have again driven home, powerfully, the existential need for urgent action to protect our planet for current and future generations,” she said.
UN High Commissioner for Human Rights Michelle Bachelet spoke with Greta Thunberg, a young environmental activist from Sweden at COP25 Madrid 2019. Credit: OHCHR Photo/Anthony Headley
Universal computing by DNA origami robots in a living animal
Figure S28: Calculation of the hemolymph space from CT scans.
A symbiotic-like biologically-driven regenerating fabric
As you can see, there is a cause-and-effect relationship between these injections and adverse reactions and deaths.
And the presence of DNA is not a contaminant
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