Ribonucleic acid (RNA) code is coming for you, cancer cells. A new Northwestern Medicine study reports that a kill code is embedded in every cell in the body whose function may be to cause the self-destruction of cells that become cancerous. As soon as the cell’s inner bodyguards sense it is mutating into cancer, they punch in the kill code to extinguish the mutating cell.

Scientists at Northwestern University know the code is triggered by chemotherapy, but they’ve learned enough about the code to trigger it without chemo. They believe this finding could lead to new therapies.

“My goal was not to come up with a new artificial toxic substance,” said lead author Marcus Peter, Ph.D., a professor of cancer metabolism at Northwestern’s Feinberg School of Medicine, in a statement. “I wanted to follow nature’s lead. I want to utilize a mechanism that nature developed.”

This builds on Peter’s prior work. In research Peter published last year, he showed that cancer cells treated with toxic RNA molecules don’t become resistant, because genes that the cells need to survive also die.

That mechanism involves six nucleotides in small RNAs. Peter’s team tested 4,096 combinations of nucleotide bases in those RNAs and hit on one that seems to be the most toxic to cancer cells. Separately, they discovered that a gene that promotes the growth of cancer cells gets chopped into pieces that act like cancer-killing microRNAs.

Although much of the excitement in oncology research of late has focused on immunotherapy, there is still significant interest in improving chemotherapy—or replacing it with drugs that confer its benefits without its harmful side effects. Startup Ascentage, for example, recently raised $150 million to advance its pipeline of drugs that work by promoting apoptosis, or programmed cell death, in cancer cells.

Zombie Gene

Killer code is not the only threat to cancer. Three years ago, oncology researchers discovered that elephants have 20 copies of p53, a gene that’s essential to cancer suppression. Humans, by contrast, have just one copy of p53. The researchers, which included a team at the University of Chicago, concluded that elephants are especially resistant to cancer because of p53—but they didn’t know the exact mechanism by which the tumor suppressor gene works.

Now the Chicago team has uncovered a key part of that process: a nonfunctioning, or “zombie” gene. The gene, called LIF6, is activated in elephants by p53, after which it kills cancer precursor cells. They believe that the discovery, which they described in the journal Cell Reports, could boost efforts to develop drugs for people that target p53.

Cells that are unable to repair DNA damage often go on to become cancerous. Elephants are estimated to have 100 times as many of these cancer precursor cells than people do, but less than 5% of captive elephants end up dying from the disease. The scientists discovered that in elephants, LIF6 makes a protein that zooms to the damaged cells’ mitochondria, or energy center, and pokes holes in it, which causes cell death.

“When [LIF6] gets turned on by damaged DNA, it kills that cell, quickly,” said senior author Vincent Lynch, Ph.D., assistant professor of human genetics at the University of Chicago, in a university press release. Lynch believes that the strategy employed by elephant cells to reawaken LIF6 could be translated to human oncology.

Interest in p53 research remains high. Startup PMV Pharma raised $74 million from venture capitalists last year to develop a pipeline of p53-targeted cancer drugs. Its approach is to use small molecules to restore the function of the gene in cancers marked by p53 mutations.

Aileron, which raised $56 million in an IPO last summer, is also targeting p53 with its lead product candidate, ALRN-6924. It’s designed to reactivate p53 tumor suppression by targeting two proteins. The drug is in early-stage clinical trials for advanced solid tumors and blood cancers.

For more information, check out:

Discovery of Cancer “Kill Code” Could Inspire New Treatments

How Elephants Resist Cancer by Reviving a “Zombie” Gene

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Ryan Lahti is the managing principal of OrgLeader and author of The Finesse Factor: How to Build Exceptional Leaders in STEM Organizations being published in early 2019. Stay up to date on Ryan’s STEM organization tweets here: @ryanlahti

(Photo: Gene, Pixabay)

What do stem cells, jaw bones, and salamanders have in common? They all have played a part in the recent advancements in regenerative medicine. As the Mayo Clinic points out, regenerative medicine itself isn’t new — forms of regenerative medicine such as the first bone marrow and solid-organ transplants were done decades ago. But advances in developmental and cell biology, immunology, and other fields have unlocked new opportunities to refine existing regenerative therapies and develop novel ones.

Mayo’s Center for Regenerative Medicine explains that regeneration involves delivering specific types of cells or cell products to diseased tissues or organs, where they will ultimately restore tissue and organ function. This can be done through cell-based therapy or by using cell products, such as growth factors. Bone marrow transplants are an example.

Stem cells are a key component of regenerative medicine, as they open the door to new clinical applications. Stem cells have the ability to develop — through a process called differentiation — into many different types of cells, such as skin cells, brain cells, lung cells and so on. Consequently, regenerative medicine holds the promise of definitive, affordable healthcare solutions that heal the body from within. Recent work done at Columbia University and the University of New South Wales (UNSW) in Australia is close to making this promise a reality.

Columbia College of Dental Medicine researchers have identified stem cells that can make new cartilage and repair damaged joints. The cells reside within the temporomandibular joint (TMJ), which articulates the jaw bone to the skull. When the stem cells were manipulated in animals with TMJ degeneration, the cells repaired cartilage in the joint.

“This is very exciting for the field because patients who have problems with their jaws and TMJs are very limited in terms of clinical treatments available,” said Mildred C. Embree, DMD, PhD, assistant professor of dental medicine at Columbia and the lead author of the study. Dr. Embree’s team, the TMJ Biology and Regenerative Medicine Lab, conducted the research with colleagues including Jeremy Mao, DDS, PhD, the Edwin S. Robinson Professor of Dentistry (in Orthopedic Surgery) at Columbia.

In a series of experiments, Dr. Embree and her colleagues isolated fibrocartilage stem cells (FCSCs) from the joint and showed that the cells can form cartilage and bone, both in the laboratory and when implanted into animals. Ultimately, Dr. Embree and her team say, the findings could lead to strategies for repairing fibrocartilage in other joints, including the knees and vertebral discs.

At UNSW in Australia, breakthrough research could make stem cell therapies capable of regenerating any human tissue damaged by injury, disease or aging available within a few years. The repair system, similar to the method used by salamanders to regenerate limbs, could be used to repair everything from spinal discs to bone fractures, and has the potential to transition current treatment approaches to regenerative medicine.

Study lead author, hematologist and UNSW Associate Professor John Pimanda, said the new technique reprograms bone and fat cells into induced multipotent stem cells (iMS). The technique has been successfully demonstrated in mice.

“This technique is ground-breaking because iMS cells regenerate multiple tissue types,” Associate Professor Pimanda said.

Prior to the UNSW research, no adult stem cells have been found that are capable of regenerating multiple tissue types. Typical adult stem cells are problematic, because they are tissue-specific. Embryonic stem cells can generate every type of cell in the human body, but they have challenges in therapeutic applications.

The UNSW study’s first author, Dr. Vashe Chandrakanthan, who developed the technology, said the new technique is an advance on other stem cell therapies being investigated. The reason is these other therapies have a number of deficiencies.

“Embryonic stem cells cannot be used to treat damaged tissues because of their tumor-forming capacity. The other problem when generating stem cells is the requirement to use viruses to transform cells into stem cells, which is clinically unacceptable,” explained Dr. Chandrakanthan.

“We believe we’ve overcome these issues with this new technique. We are currently assessing whether adult human fat cells reprogrammed into iMS cells can safely repair damaged tissue in mice, with human trials expected to begin in late 2017,” Associate Professor Pimanda said.

As the work at Columbia and UNSW show, advancements in stem cell technology can produce bone and cartilage as well as approximate how salamanders repair limbs. This work broadens the potential of regenerative medicine to treat joint and spine problems and accelerate recovery following complex surgeries where bones and joints are involved.

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Ryan Lahti is the founder and managing principal of OrgLeader, LLC. Stay up to date on Ryan’s STEM-based organization tweets here: @ryanlahti

(Photo: Stem Cell, Pixabay)

If you thought that drones could be used as a new way to deliver organ transplants, then you are thinking along the same lines as Lung Biotechnology. This month Lung Biotechnology has agreed to partner with aerial technology company EHang Holdings Limited to develop and purchase up to 1,000 units of the world’s first autonomous drone for humans (EHang’s 184 drone) to automate organ transplant delivery. The two companies have agreed to work together over the course of the next fifteen years to optimize the rotorcraft for organ deliveries, a program which they are calling the Manufactured Organ Transport Helicopter (MOTH) system.

Lung Biotechnology specializes in manufacturing lungs and other organs for transplant using a variety of technologies, including pig-to-human xenotransplantation, as well as regenerating them from stem cells. It plans to station the MOTH rotorcrafts outside of its organ manufacturing facilities. The rotorcrafts would use preprogrammed flight plans to hospitals and re-charging pads within the MOTH radius so that the manufactured organs can be delivered within their window of viability.

Currently, organ transplants are limited by the number of donors, which results in thousands of potential recipients passing away each year. In the case of lung transplants, only 2,000 lung procedures are performed annually, whereas over 200,000 people in the U.S. die of end-stage lung disease during this time period. The prospect of manufactured lungs could eliminate this numerical limit, and delivering them autonomously via the all-electric MOTH technology is expected to save the healthcare system millions of dollars with a dramatically reduced carbon footprint. MOTH purchases by Lung Biotechnology will be contingent upon successful development and U.S. Federal Aviation Administration approval of the MOTH rotorcraft, as well as approval by the U.S. Food and Drug Administration of Lung Biotechnology’s xenotransplantation organ products.

“The well-known locations of transplant hospitals and future organ manufacturing facilities makes the EHang technology ideal for Highway-In-The-Sky (HITS) and Low-Level IFR Route (LLIR) programs,” said Martine Rothblatt, Ph.D., Chairman and CEO of Lung Biotechnology. “We anticipate delivering hundreds of organs a day, which means that the MOTH system will help save not only tens of thousands of lives, but also many millions of gallons of aviation transport gasoline annually.”

The rotorcraft Ehang and Lung Biotechnology are working on isn’t a pipe dream. Autonomous rotorcraft are one of the most promising avenues for delivering critical supplies in congested urban areas or disaster zones. The MOTH rotorcraft is an autonomous drone capable of carrying a passenger more than 10 miles through the air at speeds up to 65 miles per hour by entering a destination into its accompanying smartphone app.

According to The Verge, drones have been in testing over the last few years to speed the delivery of critical medicine and supplies. A test flight to a medical clinic in West Virginia marked the first FAA-approved instance of drone delivery in the US, and Airbus has partnered with LocalMotors to crowdsource the design of a next generation medical drone. Matternet, another drone delivery startup, has been airdropping medicine and supplies for a few years.

Since drones are already being tested for the delivery of medicine and supplies, drone delivery of organ transplants seems like a potential next step. Nonetheless, there are a few hurdles to overcome. First the drones need to be built and then the legalities need to be worked out so that they can be used.

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Ryan Lahti is the founder and managing principal of OrgLeader, LLC. Stay up to date on Ryan’s STEM-based organization tweets here: @ryanlahti

(Photo: EHang 184, Flickr)

Johnson & Johnson (J&J), Takeda Pharmaceutical and venture capital firm OrbiMed have helped Israel break life science fundraising records through key investments such as establishing a biotech incubator. The biotech incubator, FutuRx, is the fruit of many months of work by Johnson & Johnson Innovation (the research development arm of J&J) along with Takeda and OrbiMed.

J&J and its partners have pledged more than $28 million to fund companies with the emphasis on early-stage biopharma companies that might not have been able to obtain financing through regular channels. This continues the trend of foreign investment in Israel. Data from IVC Research Center show Israeli life science companies pulled in $801 million last year, a 55 percent increase from the previous high. J&J has had a lengthy presence in Israel dating back to 1997 when the company bought Haifa-based Biosense, which has about 100 employees in Israel.

The first two members of FutuRx are Hepy Biosciences Ltd. and XNovo Ltd. FutuRx CEO, Dr. Einat Zisman, explained that these two companies are integral to the vision of the biotech revolution that will “develop potentially transformative new medicines.” Hepy Biosciences Ltd. is developing a candidate drug that inhibits a specific enzyme activity to stop tumor growth and metastasis. The drug will be considered for pancreatic and lung cancers as well as other potential indications. XoNovo is developing a candidate drug targeting a protein implicated in several neurodegenerative diseases, including Alzheimer’s disease and Batten Disease (a rare, fatal disorder of the nervous system that typically begins in childhood).

“A key aim of Johnson & Johnson Innovation is to find novel ways of advancing the most promising early stage science,” said Patrick Verheyen, Head of Johnson & Johnson Innovation, London. “The formation of the new biotechnology incubator in Israel is the product of an important collaboration between government, industry and venture capital that demonstrates a multi-partner approach in practice. The collaboration provides a unique platform to support and advance new companies with not only funding, but also strategic advice from both venture capital and industry pharmaceutical development experts.”

For more information, see Start-Up Israel and Fundraising Record.

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Ryan Lahti is the founder and managing principal of OrgLeader, LLC. Stay up to date on Ryan’s STEM-based organization tweets here: @ryanlahti

(Photo: Pipette, Flickr)

• Highly similar with fingerprint-like similarity: Copycat drug meets a highly-sensitive, statutory standard for similarity
• Highly similar: Copycat drug meets the statutory standard for similarity
• Similar: Copycat drug requires more studies to see whether changes in manufacturing help to show similarity
• Not similar: Copycat drug does not measure up to the original

In a best-case scenario, developers of biosimilars would only need to perform targeted animal or human studies to demonstrate their drugs match the original ones. The knockoff drugs that are dissimilar to the original drugs would not receive further consideration unless changes are made to their manufacturing processes.

While the FDA continues to clarify its treatment of biosimilars, the anticipated billion-dollar market for these biosimilars continues to be in a “hurry up and wait” mode. Because of this potential market, a number of producers of established drugs (e.g., Amgen and Biogen Idec) have gone on offense by beginning to invest in the manufacturing of their own biosimilars.

In order to read the FDA’s draft guidance, click here: FDA Draft Guidance

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Ryan Lahti is the founder and managing principal of OrgLeader, LLC. Stay up to date on Ryan’s STEM-based organization tweets here: @ryanlahti