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Neuralink's GMO-BCI patent, congressional $15B call to catch up to China, Onego Bio’s first commercial-scale pilot runs, Roche’s SBX sequencing, Yes to Orchid babies!, Valley DAO's EIR
Neuralink’s GMO-BCI patent
In US20230077899A1, the Neuralink team proposes to use genetically modified neurons as the bridge between the host’s brain, and the signal processor. Not only could these neurons act as sensors, but they could stimulate neuronal activity, even at single-cell resolution! In other words, N2 may insert a brain into your brain 🤯.
When neurons fire, intracellular Ca²⁺ levels rise. To read this activity, they built GCaMP, a fusion protein of GFP, calmodulin (which binds calcium), and M13 (which increases fluorescent response). To write neuronal activity, they encoded Channelrhodopsin-2 (ChR2), a light-sensitive ion channel that opens when exposed to blue light, triggering action potentials.
Four designs are described: A) reading neural activity with an external two-photon microscope through a transparent cranial window; B) placing an ECoG array directly on top of L0 cells; C) pre-attaching the engineered cells to the ECoG electrodes before implantation; or D) embedding the cells in a hydrogel before implantation, allowing for spatial organization, vascular access, and drug delivery.
When mice received sensory stimuli like whisker deflection, the grafted cells responded with measurable optical signals, confirming their ability to read brain input. In go/no-go reward-based experiments, mice responded to optogenetic activation, proving that the signals were interpretable and actionable.
Congressional $15B call to catch up to China
“If you want to see the future of biotech, go to iGEM” say American synthetic biologists. If you went to iGEM in the last 10 years, you know China has secured its place as the third country with the most Grand Prizes across all divisions throughout the last decade, and they’re getting ‘em started early, ranking number one in the high school division.
But I wouldn’t use iGEM as a data point in this context either. Instead, take rising number of trials (particularly in phase I, oncology, cell and gene therapy) started in China versus other leading countries. Take Pfizer’s $1 billion investment into China over the next five years. Take the 2015 regulatory reforms that made Legend Biotech go into clinical trials two years after its foundation and close a deal with J&J one year after trials. Alex Telford has a great piece on this.
Senator Todd Young highlights “In some areas of biology, they’ve already surpassed us. In other areas, on current trend lines, they will pass us… China has had a plan for two decades, we don’t have a plan”. Now, the plan for now includes the establishment of a National Biotech Coordination Office, simplifying regulations for product commercialization, biodata security, and cultivation of foreign talent.
Onego Bio’s first commercial-scale pilot runs
Speaking of biomanufacturing… while global egg production has almost doubled in volume during the past 20 years to be a market worth 35.2 billion, in early 2022, HPAI alias the bird flu led to the culling of millions of egg-laying hens, reducing supply and thus raising prices all over the world. For instance, in the US the average cost of a dozen Grade A eggs rose from $2.17 in January 2022 to $5.10 a year later, marking a 135% increase.
Onego can make proteins like ovalbumin (54% of all protein in egg whites) through genetically modified fungi called Trichoderma grown in bioreactors. They purify the egg protein and dry the liquid into a powder form that they’ve filed for GRAS and are now producing at their Wisconsin facility.
Before cofounding Onego, Dr. Landowski, worked for over 15 years at VTT on the development of T. reesei as a production host. He is one of the authors for one of their patents, which aims at increasing secretion of N-glycan proteins in filamentous fungi by mutating protease genes, expressing a heterologous oligosaccharyl transferase, and increasing alpha-1,2 mannosidase activity.
VTT is a Finnish-state owned research institution founded in 1942 that advances the commercialization of (bio)technologies. They’ve spun off more than 50 companies and work across many different sectors outside biotech. Their business areas are carbon neutral solutions, sustainable products and materials, and digital technologies. raise 10 million euros in seed funding to commercialize the breakthrough technology.
Roche’s SBX sequencing
18 years ago, a powerful duo of a Mechanical Engineer and a Biochemist started a company on a mission to create ULTRA-low-cost genome sequencing technology for the world. Allan Stephan and Mark Kokoris would lead Stratos Genomics for over a decade. They got investment and started doing research projects for Roche Diagnostics in 2014, filed their first patent for Sequencing By eXpansion (SBX) in 2015, and got acquired by Roche in 2020 — could China have bio/acc’d it?
In February of this year, Roche Sequencing announced SBX as their new proprietary sequencing technology. It can read 7 genomes in 1 hour at >30x, with read lengths spanning 50 to >1000bp, reaching F1 scores of >99.80% (SNV) and >99.56% (InDel) for HG001 whole genome samples. How ULTRA-low-cost is yet to be disclosed. The premise for now is a high-throughput, high-precision, and PCR-free, long read sequencing platform.
In a nutshell, the team engineered a special kind of polymerase, XP synthase, that synthesizes a surrogate molecule made of expanded nucleotides, X-NTPs, into the template strand. Each X-NTP has a tether between the base and the α-phosphate that acts as a different high-signal reporter for each base. At the center of each reporter is a translocation control element, TCE, that modulates movement through the nanopore.
After X-NTP synthesis, a reagent degrades the DNA template and the cleavable bond between each of the X-NTPs is broken, allowing the backbone to expand into a molecule 50X longer than the template: the expandomer. The TCE holds the reporter in the nanopore and the reporter codes are measured via a CMOS-based array, each of which contains roughly eight million microwells with one nanopore each. Finally, a short high voltage pulse is applied, and the expandomer is advanced to the next reporter.
Yes to Orchid babies!
Orchid helps families select healthy embryos by providing them a WGS service during the IVF process. They do monogenic screening for autism, intellectual disability, epilepsy, pediatric and adult-onset cancers, vision and hearing loss, and chromosomal abnormalities, as well as genetic predisposition screening for bipolar disorder, schizophrenia, Alzheimer’s disease, cancers, etc.
As a starter, simply selecting female instead of male embryos would reduce the risk for diseases such as schizophrenia, heart disease, stroke and diabetes. At a population level, some claim it may even reduce crime rates — SciFi plug: imagine human matriarchal societies that reproduce themselves via engineered iPSCs, no men required.
Here’s my ethical standpoint: condoms prevent millions of potential babies from coming into existence; surrogacy enables thousands of babies to be born each year. Both of these are ‘unnatural’ in their own way. Both have been condemned by different social groups for disrupting traditional gender roles and ‘natural’ reproduction. Both reproductive technologies are now widely accepted around the world.
Soon, I suspect, the term “having kids” may evolve into the more accurate “creating life”. Not only will it involve selection, design, and thus intention, but also imagination — Forgive me, future families, if this is still inappropriate or unethical thinking in a decade or five from now, for I can’t help but wonder whether my kids could be “my” greatest work of art. My pure intention is for you to be healthy, happy, creative, free, and zealous beings.
Join Valley DAO as an Entrepreneur in Residence
Are you an entrepreneurial biotech expert ready to transform state-of-the-art computational biology research into a startup venture?
ValleyDAO is seeking a Part-Time Entrepreneur in Residence (EIR) to evaluate the commercial viability of a computational biology platform designed for strain engineering and metabolic engineering. You will work closely with the research team to explore how this innovative software can make the leap from lab to market.
Even if this particular role is not of interest, you should totally check out more of Valley DAO’s projects if you’re interested in climate biotech or biomanufacturing. I met Albert in 2021 at the time when DAOs were super sexy and it’s great to see they didn’t just ride the hype but are actually growing something great out of it for the long term!