Lifeboat Foundation

If used to make non-heritable genetic changes, CRISPR gene-editing technology holds tremendous promise for treating or curing a wide range of devastating disorders, including sickle cell disease, vision loss, and muscular dystrophy. Early efforts to deliver CRISPR-based therapies to affected tissues in a patient’s body typically have involved packing the gene-editing tools into viral vectors, which may cause unwanted immune reactions and other adverse effects.

Now, NIH-supported researchers have developed an alternative CRISPR delivery system: nanocapsules. Not only do these tiny, synthetic capsules appear to pose a lower risk of side effects, they can be precisely customized to deliver their gene-editing payloads to many different types of cells or tissues in the body, which can be extremely tough to do with a virus. Another advantage of these gene-editing nanocapsules is that they can be freeze-dried into a powder that’s easier than viral systems to transport, store, and administer at different doses.

In findings published in Nature Nanotechnology [1], researchers, led by Shaoqin Gong and Krishanu Saha, University of Wisconsin-Madison, developed the nanocapsules with specific design criteria in mind. They would need to be extremely small, about the size of a small virus, for easy entry into cells. Their surface would need to be adaptable for targeting different cell types. They also had to be highly stable in the bloodstream and yet easily degraded to release their contents once inside a cell.

TVs and radios blare that “artificial intelligence is coming,” and it will take your job and beat you at chess.

But AI is already here, and it can beat you — and the world’s best — at chess. In 2012, it was also used by Google to identify cats in YouTube videos. Today, it’s the reason Teslas have Autopilot and Netflix and Spotify seem to “read your mind.” Now, AI is changing the field of synthetic biology and how we engineer biology. It’s helping engineers design new ways to design genetic circuits — and it could leave a remarkable impact on the future of humanity through the huge investment it has been receiving ($12.3b in the last 10 years) and the markets it is disrupting.

Researchers have developed soft robotic devices driven by neuromuscular tissue that triggers when stimulated by light—bringing mechanical engineering one step closer to developing autonomous biobots.

In 2014, research teams led by mechanical science and engineering professor Taher Saif and bioengineering professor Rashid Bashir at the University of Illinois worked together to developed the first self-propelled biohybrid swimming and walking biobots powered by beating cardiac muscle cells derived from rats.

“Our first swimmer study successfully demonstrated that the bots, modeled after sperm cells, could in fact swim,” Saif said. “That generation of singled-tailed bots utilized cardiac tissue that beats on its own, but they could not sense the environment or make any decisions.”

“DNA is like a computer program but far, far more advanced than any software ever created.” Bill Gates wrote this in 1995, long before synthetic biology – a scientific discipline focused on reading, writing, and editing DNA – was being harnessed to program living cells. Today, the cost to order a custom DNA sequence has fallen faster than Moore’s law; perhaps that’s why the Microsoft founder is turning a significant part of his attention, and wallet, towards this exciting field.

Bill Gates is not the only tech founder billionaire that sees a parallel between bits and biology, either. Many other tech founders – the same people that made their money programming 1s and 0s – are now investing in biotech founders poised to make their own fortunes by programming A’s, T’s, G’s and C’s.

The industry has raised more than $12.3B in the last 10 years and last year, 98 synthetic biology companies collectively raised $3.8 billion, compared to just under $400 million total invested less than a decade ago. Synthetic biology companies are disrupting nearly every industry, from agriculture to medicine to cell-based meats. Engineered microorganisms are even being used to produce more sustainable fabrics and manufacture biofuels from recycled carbon emissions.

Bioengineers and life scientists incorporate hybridoma technology to produce large numbers of identical antibodies, and develop new antibody therapeutics and diagnostics. Recent preclinical and clinical studies on the technology highlight the importance of antibody isotypes for therapeutic efficacy. In a new study, a research team in Netherlands have developed a versatile Clustered Regularly Interspaced Short Palindrome Repeats (CRISPR) and homology directed repair (HDR) platform to rapidly engineer immunoglobin domains and form recombinant hybridomas that secrete designer antibodies of a preferred format, species or isotype. In the study, Johan M. S. van der Schoot and colleagues at the interdisciplinary departments of immunology, proteomics, immunohematology, translational immunology and medical oncology, used the platform to form recombinant hybridomas, chimeras and mutants. The stable antibody products retained their antigen specificity. The research team believes the versatile platform will facilitate mass-scale antibody engineering for the scientific community to empower preclinical antibody research. The work is now published on Science Advances.

Monoclonal antibodies (mAb) have revolutionized the medical field with applications to treat diseases that were once deemed incurable. Hybridoma technology is widely used since 1975 for mAb discovery, screening and production, as immortal cell lines that can produce large quantities of mAbs for new antibody-based therapies. Scientists had generated, validated and facilitated a large number of hybridomas in the past decade for preclinical research, where the mAb format and isotypes were important to understand their performance in preclinical models. Genetically engineered mAbs are typically produced with recombinant technology, where the variable domains should be sequenced, cloned into plasmids and expressed in transient systems. These processes are time-consuming, challenging and expensive, leading to outsourced work at contract research companies, which hamper the process of academic early-stage antibody development and preclinical research.

In its mechanism of action, the constant antibody domains forming the fragment crystallizable – (Fc) domain are central to the therapeutic efficacy of mAbs since they engage with specific Fc receptors (FcRs). Preceding research work had highlighted the central role of Fc in antibody-based therapeutics to emphasize this role. Since its advent, CRISPR and associated protein Cas-9 (CRISPR-Cas9)-targeted genome editing technology has opened multitudes of exciting opportunities for gene therapy, immunotherapy and bioengineering. Researchers had used CRISPR-Cas9 to modulate mAb expression in hybridomas, generate a hybridoma platform and engineer hybridomas to introduce antibody modification. However, a platform for versatile and effective Fc substitution from foreign species within hybridomas with constant domains remains to be genetically engineered.

Ira Pastor, ideaXme longevity and aging ambassador and founder of Bioquark, interviews James Strole, Co-Founder and Co-Director of People Unlimited and Director of the Coalition For Radical Life Extension.

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