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BGRF and SILS Scientists Analyze Viability of shRNA Therapy for Huntington’s Disease – Press Release by Biogerontology Research Foundation

BGRF and SILS Scientists Analyze Viability of shRNA Therapy for Huntington’s Disease – Press Release by Biogerontology Research Foundation

Biogerontology Research Foundation


Friday, December 1, 2017, London, UK: Researchers from the Biogerontology Research FoundationDepartment of Molecular Neuroscience at the Swammerdam Institute for Life Sciences at the University of Amsterdam, and the Department of Neurobiology, Care Sciences and Society at the Karolinska Institute announce the publication of a paper in Translational Neurodegeneration, a BioMedCentral journal, titled RNAi mechanisms in Huntington’s disease therapy: siRNA versus shRNA.

After many years of development, RNAi therapeutics are nearing the clinic. There are several variants on RNAi therapeutics, such as antisense oligonucleotides (ASOs), short-hairpin RNA (shRNA), small interfering RNA (siRNA), et cetera. The researchers’ paper aimed to answer the question of why RNAi therapeutics for nucleotide repeat disorders (specifically Huntington’s, a devastating genetic neurodegenerative disease), have lost favor in recent years. After a phenomenal amount of excitement, these therapies were hindered by problems like molecular stability, dosing, and transcriptional control of the gene therapeutic construct.

“We compared various RNAi-based therapeutic modalities available for the treatment of Huntington’s Disease and offered mechanistic proposals on how to break through current barriers to clinical development. One key problem has proven to be modulating the expression level of shRNA constructs, which would otherwise be the clear frontrunner among ASOs, siRNAs, and other methods due to duration of expression, dramatically reduced off-target effects, and ease of delivery by adeno-associated viruses that are already approved by the EMA and FDA. We also put forward novel methods of modulating construct expression and avoiding off-target effects” said Franco Cortese, co-author of the paper and Deputy Director of the Biogerontology Research Foundation.

The researchers analyzed available data on the levels of off-target effects associated with siRNA vs shRNA, surveyed emerging strategies to reduce off-target effects in shRNA therapies (such as tough decoy RNAs, or TuDs), and proposed novel methods of controlling shRNA expression, in particular through the use of negative feedback-driven oscillating promoters.

Mechanism of TFEB at the PGC1-a promoter. The PGC1a promoter contains a CLEAR-box that is known to be bound by TFEB, a transcription factor induced during autophagy and lysosomal biogenesis. A construct being the PGC1a promoter CLEAR-box would be induced by TFEB under conditions of intracellular proteotoxicity due to HTT aggregation. By this mechanism, on-demand suppression of HTT could be achieved | Credit: Translational Neuroscience

 

“We proposed two novel feedback mechanisms that 1) activate construct expression stoichiometrically with mutant Huntingtin expression, or 2) only during aggregate-induced autophagy and lysosomal biogenesis. That way, the problem of excessive construct expression may be mitigated. These ideas were inspired by feedback systems used in synthetic biology, and in ‘nonsynthetic,’ naturally occurring biological systems” said Sebastian Aguiar, lead author of the paper.

Readers can read the open-access paper here: https://translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-017-0101-9.

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About the Biogerontology Research Foundation

The Biogerontology Research Foundation is a UK non-profit research foundation and public policy center seeking to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF funds and conducts research which, building on the body of knowledge about how ageing happens, aims to develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce the effective, lasting treatments for the diseases and disabilities of ageing, required to improve quality of life in the elderly. The BGRF seeks to use the entire scope of modern biotechnology to attack the changes that take place in the course of ageing, and to address not just the symptoms of age-related diseases but also the mechanisms of those diseases.

About the Swammerdam Institute for Life Sciences

The Swammerdam Institute for Life Sciences (SILS) is the largest institute of the Faculty of Science at the University of Amsterdam. The institute comprises biological disciplines including molecular and cell biology, microbiology, plant science, physiology and neurobiology, supported by modern enabling technologies for the life sciences. The research groups of SILS also develop methods in genomics (micro-array, next-gen sequencing, proteomics), bioinformatics and advanced light microscopy technologies. Knowledge from adjacent fields of science, in particular biochemistry, biophysics, medicine, bioinformatics, statistics and information technology make SILS a multidisciplinary research institute with a systems biology approach to the life sciences. SILS’ research objective is to understand the functioning of living organisms, from the most basic aspects up to complex physiological function(s). Biological processes are studied at the level of molecules, cells, cellular networks and organisms. SILS research topics have in common that similar cellular processes and interactions are studied, likewise using similar methodologies and technologies. Therefore SILS scientists often study the same concepts in different biological systems. Within the institute, this leads to exchange of information and extension of research over the borders of different disciplines. Part of SILS research activities are directed to application-oriented research in close collaboration with industry.

Shibuya Mirai, The First AI Bot Granted Official Residency – Article by B.J. Murphy

Shibuya Mirai, The First AI Bot Granted Official Residency – Article by B.J. Murphy

B.J. Murphy


A few days ago, an artificial intelligence (AI) bot was granted official residency in Shibuya, a Tokyo ward with a population of around 224,000 people. The AI bot’s name is “Shibuya Mirai,” which takes the form of a seven-year-old boy, and serves as a chatbot on the popular Line messaging app.

According to Japan Today:

“Tokyo’s Shibuya Ward, an area popular with fashion-conscious young people, has given the character his own special residence certificate. This makes him Japan’s first, and maybe the world’s first, artificial intelligence bot to be granted a place on a real-life local registry.”

Mirai, whose name translates to “future,” is part of a project aimed at making the local government more familiar and accessible to locals, according to the ward, and is designed to listen to the opinions of Shibuya residents.

Image source: Shibuya City

Nearly two weeks ago, Sophia, a humanoid robot designed by Hong Kong company Hanson Robotics, was granted citizenship by the Kingdom of Saudi Arabia, becoming the world’s first humanoid robot to ever be granted such an honor. And just as the U.S. Transhumanist Party supported Sophia’s citizenship recognition, we also would like to congratulate Mirai as well, along with the Shibuya Ward and Microsoft in their joint-development of the AI bot.

In accordance with the U.S. Transhumanist Party Constitution Article III, Section IX [Adopted by a vote of the members during February 16-22, 2017]:

“The United States Transhumanist Party supports all emerging technologies that have the potential to improve the human condition – including but not limited to autonomous vehicles, electric vehicles, economical solar power, safe nuclear power, hydroelectricity, geothermal power, applications for the sharing of durable goods, artificial intelligence, biotechnology, nanotechnology, robotics, rapid transit, 3D printing, vertical farming, electronic devices to detect and respond to trauma, and beneficial genetic modification of plants, animals, and human beings.”

While we recognize, to the best of our ability, that Mirai is still nowhere close to being deemed sentient – rather operates as a narrow AI – we equally recognize the significance of granting an AI real-life residency during a time when artificial general intelligence (AGI) research is at an all-time high.

It has been predicted that an AGI could possibly emerge within the next decade or so. Preparing the framework for both AI and robot rights in our near future is absolutely crucial. We are hopeful that, with Mirai being granted official residency, we are moving in a positive direction where all sentient lifeforms of the future (whether they be human, robot, AI, or otherwise) will be able to live and strive together peacefully.

B.J. Murphy is Director of Social Media for the U.S. Transhumanist Party.

Statement on the Catalonia Independence Referendum Vote and Spanish Government’s Response

Statement on the Catalonia Independence Referendum Vote and Spanish Government’s Response

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B.J. Murphy


On October 1, the autonomous community of Catalonia came together to vote for the future of its independence from that of the Kingdom of Spain. While the referendum was initially peaceful, chaos began to ensue once the Constitutional Court of Spain gave the order for police to raid Catalan government buildings and spots known where the referendum would be held, after having determined that the referendum is illegal.

In response, the Catalan people began protesting the police raids, demanding for recognition of their votes and for Catalan independence. Even the Mayor of Barcelona, Ada Colau, took to Twitter to condemn the raids, stating, “A cowardly president has filled our city with police. Barcelona, city of peace, is not afraid.”

Despite heavy crackdown and reported police brutality of the protesters, 42% of the autonomous community was able to successfully cast their vote, including Catalan president, Carles Puigdemont. The results: 90% voted in favor of independence.

And while King Felipe VI has since made a rare televised statement on the matter, accusing Catalan leaders of “unacceptable disloyalty,” Catalan president, Carles Puigdemont, has officially determined that his government would unilaterally declare independence by “the end of this week or the beginning of next,” according to BBC.

While United States Transhumanist Party has no official declaration of support for other foreign general regions to secede from their respective countries, according to Article III, Section XXXI of our Constitution, it states:

“The United States Transhumanist Party supports the right of any jurisdiction to secede from the United States specifically in opposition to policies that institutionalize racism, xenophobia, criminalization of dissent, and persecution of peaceful persons. The United States Transhumanist Party does not, however, condone any secession for the purposes of oppressing others. Therefore, the secession of the Confederate States in 1860 was illegitimate, but a future secession of a State may be justified in reaction to violent crackdowns by the federal government against individuals based on individuals’ national origin or ancestry.”

As such, we firmly believe that a similar moral principle should be extended to the people of Catalonia who peacefully voted for independence from the Kingdom of Spain. We condemn the actions of King Felipe and the Spanish government for attempting to violently suppress the Catalan people’s right to democracy and to peacefully protest when the former is withheld.

Given our own country’s history of fighting for independence from the United Kingdom, we know all too well the lengths of which the powerful will try to demean, belittle, and oppress those who stand up to them. The events which led up to the American Revolution, too, were deemed illegal in accordance with then-British law. This gave our Founding Fathers a lot to think about as they began building this country – in particular, it was Thomas Jefferson who once declared, “If a law is unjust, a man is not only right to disobey it, he is obligated to do so.”

And so, unlike the Kingdom of Spain, we, the United States Transhumanist Party, recognize and stand in solidarity with the Catalan peoples’ quest for freedom by breaking away from the country and to become an independent nation themselves.

Ed. Note: Originally, the article had erroneously specified that King Felipe VI had given the orders for the police raids of Catalan government buildings. After further inspection, we’ve realized that, while King Felipe did appoint the magistrates of the Constitutional Court of Spain, all decisions – including that of the police raids – were given independently by the Court itself. Our statement has been refined to accommodate this change of information.

B.J. Murphy is the Director of Social Media for the U.S. Transhumanist Party.

MouseAge: Using Artificial Intelligence to Determine Age and Assess Therapies Against Aging – Project by Lifespan.io

MouseAge: Using Artificial Intelligence to Determine Age and Assess Therapies Against Aging – Project by Lifespan.io

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United States Transhumanist Party


According to Article 3, Section V of the Constitution of the United States Transhumanist Party:

“The United States Transhumanist Party supports concerted research in effort to eradicate disease and illness that wreak havoc upon and cause death of sapient beings. We strongly advocate the increase and redirection of research funds to conduct research and experiments and to explore life, science, technology, medicine, and extraterrestrial realms to improve all sentient entities.”

Which is why the U.S. Transhumanist Party is pleased to announce the official launch of the fundraising campaign for the MouseAge project. MouseAge is a longevity-based project started by one of our Allied Organizations, Lifespan.io, of which we’ll provide relevant information below:

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Will Today’s Disabled Become Tomorrow’s First Post-Human? – Article by B.J. Murphy

Will Today’s Disabled Become Tomorrow’s First Post-Human? – Article by B.J. Murphy

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B.J. Murphy


Needs will almost always come before wants. When it comes to Transhumanism, the ability to differentiate the two tends to blur, because a need could also be a want depending on the various methods of achieving a need. There’s the “getting by” need and then there’s the “thriving” need.

For the disabled, this dichotomy determines how well they’ll get by in life. If someone loses a leg, then simply getting by could be achieved with a cane, a walker, or even a low-tech prosthetic. However, if this person wishes to thrive in life, then a high-tech prosthetic would be much more preferable, though could also be considered a want rather than a need.

For Transhumanism to work, however, I’d argue that the ability to thrive should be considered an absolute necessity. Thus when it comes to the disabled, I believe they deserve the ability to reach post-humanity before anyone else. In all actuality, this is already happening.

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The Trolley Problem and Self-Driving Vehicles – Article by B.J. Murphy

The Trolley Problem and Self-Driving Vehicles – Article by B.J. Murphy

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B.J. Murphy


One of the most popular discussions in the field of technology today is that of self-driving vehicles. It’s a topic that brings up both optimistic joy and pessimistic fear, from the elimination of car-related fatalities to the elimination of millions of jobs. I usually stand on the optimistic side of the argument, but I also understand the fear.

After all:

  • According to the Bureau of Labor Statistics (BLS), there were nearly 1.8 million heavy-truck and tractor-trailer drivers in 2014, with a 5% increase per year. Meaning, there are likely around 2 million of these drivers today.
  • There were around 1.33 million delivery truck drivers in 2014, with a 4% increase per year. Meaning, there are over 1.4 million today.
  • There were around 233,700 taxi drivers and chauffeurs in 2014, with a 13% increase per year. Meaning, there are nearly 300,000 of these drivers today.

In other words, with the full mobilization of self-driving vehicles, we’re looking at around (+/-) 4 million jobs being automated in the next few years, thus no longer requiring human labor. This particular risk, however, isn’t what I’m currently focused on. The main focus of this article is on what is known as the “trolley problem” – a thought experiment in ethics that has since been rehashed to serve as “criticism” towards self-driving vehicles.

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Would You Allow Your Children To Be Alone With a Robot? – Article by B.J. Murphy

Would You Allow Your Children To Be Alone With a Robot? – Article by B.J. Murphy

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B.J. Murphy


Would you allow your children to be alone with a robot? I ask not for the children’s safety in mind, but rather the robot’s.

As shown in the video provided above, a group of Japanese researchers – from ATR Intelligent Robotics and Communication Laboratories, Osaka University, Ryukoku University, and Tokai University – patrolled a public shopping complex in Osaka using a remotely-operated robot known as Robovie 2.

Children naturally being curious, hordes of them decide to surround the robot when spotted. Some were quite nice and simply wanted to play with the robot. However, others felt the need to attack it either by kicking, punching, or trying to rip its head off.

What I find most fascinating about this is that, like a child, whenever the robot feels like it’s in possible danger (or, rather, there’s an increased probability of danger) – of which it’s able to do so by calculating the probability of abuse based on interaction time, pedestrian density, and the presence of people above or below 4 feet 6 inches in height – the robot then changes course and brings itself within close proximity of a parent for protection.

Robots are, most certainly, coming and will potentially disrupt nearly every major industry in society. However, to ensure their overall safety, it might be best that, whenever a child comes close to one of these robots, a parent should always be nearby – not for the sake of the child, but for the sake of the robot.

Which then raises the question: what is the U.S. Transhumanist Party’s position on protecting robots from unnecessary physical abuse? For now, in accordance with the Party’s Constitution – in particular, Section XXXIII – it states:

“…Level 4 or lower-level entities – including domain-specific artificial intelligences that have not achieved sentience – may be utilized as part of the production systems of the future, in a similar manner to machines, algorithms, computer programs, and non-human animals today and based on similar ethical considerations.”

Speaking as an individual member of the U.S. Transhumanist Party, it is of my opinion that we should begin expanding upon the question of “ethical considerations” in regards to the physical abuse of robots. This shouldn’t be confused as being tantamount to giving robots, regardless of sentience, full rights as that of other sapient beings. That, too, is already addressed in Section XXXIII, which states:

“The United States Transhumanist Party stands for the rights of any sentient entities defined in the Preamble to the Transhumanist Bill of Rights as possessing Level 5 or more advanced information integration. Any such sentient entities, including new kinds of sentient entities that may be discovered or developed in the future, shall be considered to be autonomous beings with full rights, and shall not be made subservient to humans, unless they as individuals pose direct, empirically evident threats to the lives of others. The protections of full individual rights shall extend to Level 5 or higher-level artificial intelligences.”

One might think that this question could be juxtaposed with that of the question of property rights. And, to a certain degree, it would. However, when it comes to robots, we also have to consider the psychological ramifications as well. We deliberately give robots anthropomorphic features given the fact that research has shown, time and again, that, unlike other inanimate objects, robots have the ability to evoke empathetic emotional responses by humans as a result – especially when humans believe those robots are being abused.

In other words, by physically abusing robots, one is then potentially causing psychological harm to other sentient entities in consequence.

This then raises a problematic situation when simply juxtaposing non-sentient robot rights to that of property rights. Unlike other property, robots have the capability of evoking empathy out of humans. Thus my reasoning for wanting to bring this particular topic up for further discussion.

Where should Transhumanists stand – and, in particular, the U.S. Transhumanist Party – in regards to the physical abuse of robots, keeping in mind the potential psychological ramifications that may arise among humans as a direct result?

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B.J. Murphy is the Director of Social Media of the U.S. Transhumanist Party.

R.I.P. Jacque Fresco – The Mind Behind The Venus Project

R.I.P. Jacque Fresco – The Mind Behind The Venus Project

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B.J. Murphy


“If you think we can’t change the world, it just means you’re not one of those who will.”
– Jacque Fresco

In the early morning of May 18, Jacque Fresco – the visionary futurist behind The Venus Project – had passed away at the age of 101 after years of battling Parkinson’s. Although the U.S. Transhumanist Party and Mr. Fresco had somewhat differing views on how to incorporate a future transformed by advanced science and technology, his passing is a true loss for the movement as a whole.

Mr. Fresco had envisioned a future where poverty was eliminated, war was no longer heard of, religion no longer shackled the mind, and the monetary system no longer had a grip over our socio-economic foundation. Instead, this future society would be solely based on the collective management of resources with the help of automation, robotics, and artificial intelligence – what he called a “Resource-Based Economy” (RBE). This vision would later be known as The Venus Project, whereby a Research Center was constructed in Venus, Florida to serve as a case-by-example in accordance to that vision.

We should consider ourselves extremely grateful that Mr. Fresco dedicated so much time, money, and effort on this vision of his. Not only did he help build a global community devoted to the materialization of his vision, but he had also inspired countless numbers of people within the Transhumanist movement to begin thinking about how to build a better and more peaceful future.

Jacque Fresco was a pioneer, one of the last great futurists of the 20th century. To the Transhumanist movement, Mr. Fresco was a giant, as we all equally stand on his shoulders. He may have passed away, but his vision for the future will always live on.

Rest in peace, our friend. You will truly be missed by millions.

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B.J. Murphy is the Director of Social Media of the U.S. Transhumanist Party.

The Importance of 3D Printing to Ensuring the Viability of Interplanetary City Construction

The Importance of 3D Printing to Ensuring the Viability of Interplanetary City Construction

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B.J. Murphy


Starting on March 26, members of the U.S. Transhumanist Party are taking part in the latest platform vote, which include 22 potential planks in total. Before the voting ends on April 2, I’d like to briefly discuss one of those potential planks – in particular, Section E3-G. Space Colonization. To be a little more clear, I wish to present a possible solution to one distinct question we’ll likely need to ask ourselves once actual space colonization efforts are underway.

A little over a year ago, a friend and fellow author Manu Saadia (author of Trekonomics: The Economics of Star Trek) posed a question to me about the viability of creating actual cities on other planets. It was, in his mind, one of the few things about Star Trek which seemed unrealistic, because of the fact that cities here on Earth thrive due to one important reason: imports/exports, i.e. resource exchange.

I’ll quote him below on his exact phrasing:

“[S]ettling a far away colony on Mars or a bunch of habitats in orbit is not a recipe for prosperity for these space-based outposts. Without fast and reliable means of exchange, I don’t see how these settlements could take full advantage of the network effects and of the endogenous dynamism of Earth’s great cities.”

He is correct in his assessment that, without the fast import and export of necessary resources, today’s cities simply wouldn’t survive. However, as I noted to him, I believe his strict reliance on economics, and much less so on technology, prevents him from understanding how interplanetary cities are still a viable prospect.

That is, he seems to completely ignore key technologies, such as 3D printing, which would directly address the current problem of importing and exporting resources from planet to planet. My own assessment was:

“Thanks to the company Made in Space, astronauts on the ISS are able to receive digital data from Earth that activates their 3D printer to print whatever supplies they need. It’s still in its infancy, but this really isn’t all that different from Star Trek’s teleportation technology.

Once it matures, I can easily see us establishing a base of developing trade agreements between different planets via 3D printing or other advanced technologies that’ll supersede 3D printing.”

If members of the U.S. Transhumanist Party were to successfully vote in favor of Section E3-G, I believe it will be our duty in discussing all of the obstacles that stand in between us and our space colonization aspirations. This brief article here will serve as only one possible solution, for which we should all discuss and consider as a Party.

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B.J. Murphy is the Director of Social Media of the U.S. Transhumanist Party.

International Longevity & Cryopreservation Summit (ft. José Cordeiro, Aubrey de Grey and much more)

International Longevity & Cryopreservation Summit (ft. José Cordeiro, Aubrey de Grey and much more)

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B.J. Murphy


On May 26-28, Spain will host the first International Longevity Cryopreservation Summit, with Fundacion VidaPlus serving as the main organizer. In attendance will be several speakers, which will include the U.S. Transhumanist Party’s advisors Dr. Aubrey de Grey and José Luis Cordeiro, where they will discuss longevity, indefinite lifespans, cryopreservation, and other biomedical areas.

If you’re thinking of attending this momentous event, early bird tickets are still on sale at the Summit’s main website. Early bird will end by April 1, so be sure to head on over and reserve your seat.

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B.J. Murphy is the Director of Social Media of the U.S. Transhumanist Party.