Lifeboat Foundation

Gene therapy may be the best hope for curing retinitis pigmentosa (RP), an inherited condition that usually leads to severe vision loss and blinds 1.5 million people worldwide.

But there’s a huge obstacle: RP can be caused by mutations in over 80 different genes. To treat most RP patients with gene therapy, researchers would have to create a therapy for each gene—a nearly impractical task using current gene therapy strategies.

A more universal treatment may be forthcoming. Using CRISPR-based genome engineering, scientists at Columbia University Vagelos College of Physicians and Surgeons are designing a gene therapy with the potential to treat RP patients regardless of the underlying genetic defect.

Using this natural process as a basis, scientists developed a gene-editing tool called CRISPR/Cas that can cut a specific DNA sequence by simply providing it with an RNA template of the target sequence. This allows scientists to add, delete, or replace elements within the target DNA sequence. Slicing a specific part of a gene’s DNA sequence with the help of the Cas9 enzyme, aids in DNA repair.

This system represented a big leap from previous gene-editing technologies, which required designing and making a custom DNA-cutting enzyme for each target sequence rather than simply providing an RNA guide, which is much simpler to synthesize.

CRISPR gene editing has already changed the way scientists do research, allowing a wide range of applications across multiple fields. Here are some of the diseases that scientists aim to tackle using CRISPR/Cas technology, testing its possibilities and limits as a medical tool.

While during Apollo 13 the phrase “Failure is Not an Option” was coined, in life and especially for students, failure must be an option for growth. In this talk, Michelle Lucas encourages failing forward. Michelle Lucas was raised in the Chicagoland area and found a passion for space very early in her life. She studied Aerospace Engineering, Communications & Space Studies at Purdue University and Embry Riddle Aeronautical University. During this time she conducted microgravity fluids research on NASA’s KC-135 aircraft and also worked as a counselor at Space Camp in Florida. After graduation from college, Michelle spent 11 years working at NASA’s Johnson Space Center. She began on the Safety Reliability & Quality Assurance Contract as part of the Payload Safety Review Panel for experiments flying to the International Space Station. After this she worked as a Flight Controller in Mission Control for the International Space Station for the Ops Plan Group and as a Astronaut Technical Instructor in the Daily Operations Group. Additionally she worked with each of the International Partners (European Space Agency – ESA, Japanese Space Agency – JAXA and the Russian Space Agency) in the field of Daily Operations, Flight Controller and Instructor Training. Michelle was responsible for the basic instructional training of all technical instructors for in the US as well as for the ISS International Partners. Michelle was part of the Core NASA Extreme Environment Mission Operations (NEEMO) team for 9 missions where astronauts would carry out analog space missions underwater in the Aquarius habitat. Along the way, Michelle found she has a passion for exciting the next generation and founded the non-profit Higher Orbits to use space to excite and inspire students about STEM, STEAM, Leadership, Teambuilding and Communication. Higher Orbits flagship program is called Go For Launch! This program allows students work with an astronaut and other accomplished individuals in the fields of Space, STEM and STEAM. Additionally, Michelle and a business partner run uniphi space agency – a talent management company for retired astronauts. Michelle is proud to be a Space Camp Alumni and member of the Space Camp Hall of Fame and believes that collaboration in space and STEM is the key to the stars! Space Inspires! This talk was given at a TEDx event using the TED conference format but independently organized by a local community.

Wires and cables are not the only things that can get entangled: Plants, fungi, and bacteria can all exhibit filamentous or branching growth patterns that eventually become entangled too. Previous work with nonliving materials demonstrated that entanglement can produce unique and desirable material properties, but achieving entanglement requires meticulously engineered material structure and geometry. It has been unclear if the same rules apply to organisms, which, unlike nonliving systems, develop through a process of progressive growth. Through a blend of experiments and simulations, we show that growth easily produces entanglement.

Specifically, we find that treelike growth leads to branch arrangements that cannot be disassembled without breaking or deforming branches. Further, entanglement via growth is possible for a wide range of geometries. In fact, it appears to be largely insensitive to the geometry of branched trees but instead depends sensitively on how long the organism can keep growing. In other words, growing branched trees can entangle with almost any geometry if they keep growing for a long-enough time.

Entanglement via growth appears to be largely distinct from, and easier to achieve than, entanglement of nonliving materials. These observations may in part account for the broad prevalence of entanglement in biological systems, as well as inform recent experiments that observed the rapid evolution of entanglement, though much still remains to be discovered.

PHILADELPHIA — Scientists at the University of Pennsylvania’s Perelman School of Medicine have developed a new method to create human artificial chromosomes (HACs) that could revolutionize gene therapy and other biotechnology applications. The study, published in Science, describes an approach that efficiently forms single-copy HACs, bypassing a common hurdle that has hindered progress in this field for decades.

Artificial chromosomes are lab-made structures designed to mimic the function of natural chromosomes, the packaged bundles of DNA found in the cells of humans and other organisms. These synthetic constructs have the potential to serve as vehicles for delivering therapeutic genes or as tools for studying chromosome biology. However, previous attempts to create HACs have been plagued by a major issue: the DNA segments used to build them often link together in unpredictable ways, forming long, tangled chains with rearranged sequences.

The Penn Medicine team, led by Dr. Ben Black, sought to overcome this challenge by completely overhauling the approach to HAC design and delivery. “The HAC we built is very attractive for eventual deployment in biotechnology applications, for instance, where large-scale genetic engineering of cells is desired,” Dr. Black explains in a media release. “A bonus is that they exist alongside natural chromosomes without having to alter the natural chromosomes in the cell.”

Ubiquitous Potential

While many gene-editing therapies are focused on fatal genetic diseases, epigenetic editing’s safety profile may enable the treatment of more common diseases. The fact that no underlying changes are made to the DNA sequence “offers some additional safety assurances for this approach compared to some others where the risk/benefit [ratio] needs to be maybe a little different before you would employ those technologies,” Kane told BioSpace.

Additionally, because most common diseases are not driven by genetic mutations, epigenetic editing may be a better fit. “Most of those diseases are driven from expression levels being at an unhealthy level,” Kane said. “That is something that a tool like epi[genetic] editing is uniquely well-suited to address.”

During cell division, a ring forms around the cell equator, which contracts to divide the cell into two daughter cells. Together with researchers from Heidelberg, Dresden, Tübingen and Harvard, Professor Jan Kierfeld and Lukas Weise from the Department of Physics at TU Dortmund University have succeeded for the first time in synthesizing such a contractile ring with the help of DNA nanotechnology and to uncover its contraction mechanism.

The results have been published in the journal Nature Communications (“Triggered contraction of self-assembled micron-scale DNA nanotube rings”).

In synthetic biology, researchers try to recreate crucial mechanisms of life in vitro, such as cell division. The aim is to be able to synthesize minimal cells. The research team led by Professor Kerstin Göpfrich from Heidelberg University has now synthetically reproduced contractile rings for cell division using polymer rings composed of DNA nanotubes.

Acute myeloid leukemia (AML) is a rare and aggressive hematologic malignancy. AML progresses rapidly and is indicated by an excess of immature white blood cells. It is caused by high mutational burden over the span of a person’s life. One signature mutated gene includes the tumor suppressor gene TP53. Normally, TP53 helps make protein to stop oncogenesis or the formation of tumors. However, mutated TP53 loses that function and commonly results in AML. Unfortunately, those that have a TP53 mutation have an extremely aggressive tumor that is resistant to conventional chemotherapy drugs and results in poor prognosis. Other standard treatments include stem-cells transplants, and sometimes targeted drugs such as intracellular pathway inhibitors. Although many treatments are routine and help the patient reduce symptoms, there is no cure. Extensive research is currently being done by researchers and physicians to identify new approaches for AML treatment.

One novel therapy used in other hematologic malignancies includes chimeric antigen receptor (CAR)-T cell therapy. This therapy takes immune T cells (responsible for lysing or kill infections) from the patient or a donor and engineers them to target the tumor. Normally, these T cells would not recognize tumor growth, therefore, the engineered CAR-T cells are programmed to elicit an immune response and recognize surface markers on the tumor to lyse it. This therapy has been successful in other leukemias such as B-cell acute leukemia, and researchers are working to overcome treatment resistant AML using the same approach.

A recent article in EMBO Molecular Medicine, by Drs. Markus Manz, Stephen Boettcher and others, demonstrate that TP53-mutated AML is resistant to CAR-T cell therapy as a single agent, but can be overcome through combination therapy. Manz and Boettcher are principal investigators from the University of Zurich and the Department of Medical Oncology and Hematology at the University Hospital Zurich (USZ) and focus on mechanisms surrounding hematological diseases. The Zurich team first reported why TP53-mutated AML is resistant to CAR-T cell therapy. Using various models, it was noted that the engineered T cells quickly become ‘exhausted’ or inactive due to overstimulation or surrounding stimuli. The team further studied the underlying mechanism in this disease by concluding that TP53-deficient cells caused resistance through several metabolic pathways. Moreover, these pathways including the mevalonate and Wnt pathways were identified to improve therapeutic efficacy.

Researchers at Rutgers and Emory University are gaining insights into how schizophrenia develops by studying the strongest-known genetic risk factor.

When a small portion of chromosome 3 is missing—known as 3q29 deletion syndrome—it increases the risk for schizophrenia by about 40-fold.

Researchers have now analyzed overlapping patterns of altered gene activity in two models of 3q29 deletion syndrome, including mice where the deletion has been engineered in using CRIPSR, and human brain organoids, or three-dimensional tissue cultures used to study disease. These two systems both exhibit impaired mitochondrial function. This dysfunction can cause energy shortfalls in the brain and result in psychiatric symptoms and disorders.