In the August issue of “Hot Topics in Tech” newsletter series, we revisit the molecular world of CRISPR and it’s related patent activity in the agricultural sector. This issue also provides a quick foray into exciting developments in battery technology.
CRISPR Is Paving the Way for Crops of the Future
For several millennia, human beings have intelligently designed and modified plants for diverse applications. These include applications in agriculture, horticulture, and increasing the ornamental and aesthetic value of plants. Sophisticated gene editing techniques allow us to modify crops, and create new disease resistant varieties and varieties that can withstand harsh environments. Genome editing techniques can also have a positive impact on food production helping to feed starving populations. Among several gene editing tools, the most prominent one is the recent CRISPR/CAS9 system. CRISPR/CAS9 systems allow for more precise gene editing, providing a greater potential to be beneficial in crop improvement, herbicide resistance, insect and viral resistance, altered oil content in crops, delayed fruit ripening, pollen control, cold and drought tolerance, as well as providing an alternate source of energy. Agritech companies like Pairwise are also applying CRISPR to make plants even healthier, more convenient, more appealing and sustainable.
CRISPR-mediated gene editing has been demonstrated as a reliable tool in several plant species. Table 1 below summarizes a few CRISPR-based plant precise gene editing systems. Precise gene targeting efficiency was achieved in the rice ALS gene. Briefly the technique involves engineering a donor template with the desired gene sequence changes between two homologous arms. The length of the homology arms, flanking the inserted or replaced fragments, needs to be optimized in the context of the targeted genes. The donor template can be included in the plasmid containing the CRISPR cassette or built into a separate plasmid for delivery depending on the transformation method.
Tab. 1 CRISPR-Based Plant Gene Editing Systems (Source: Gene editing in Plants: Progress and Challenges)
The USA and China dominate patent filings related to gene editing in agriculture (Fig. 1). The rising dominance of China in the agricultural applications of CRISPR is likely due to the influx of investments and government support. There is uncertainty surrounding the value of CRISPR crop patents in EP following an earlier decision by European court of justice to bring them under GMO Directive. The GMO classification for CRISPR crops may translate to market difficulties for such products in Europe, reduced R&D investment and patent filings in the future.
The overall patent filing trend shows a steady increase between 2011-2014, which falls around the same time CRISPR was starting to be harnessed for its genome editing prowess by global researchers such as Siksnys, Charpentier, Doudna, and Zhang. Not surprisingly, research institutions and academia account for most of the inventions (Fig. 3). Key companies with patents include DowDupont, Monsanto, Caribou Biosciences, Syngenta, Sigma Aldrich, and Sakata Seed Corp. Many agritech companies such as DuPont, BASF, Syngenta, J.R. Simplot, Yield 10, Pioneer, Bayer, Evolva and Pairwise have already signed license agreements with major CRISPR owners thereby securing their commercial interests.
Fig. 1 Priority Countries With Count of Patent Families; EP and PCT Applications Accounted for 23 and 18 Families Respectively
Fig. 2 Patent Filing Trend Based on Earliest Priority Year; the Dip in 2018 and 2019 Is Due to Publication Lag
Fig. 3 Top Players Patent Filing Distribution
We have segmented CRISPR patenting activity according to high valued crops including maize, rice, wheat, barley, soybean and tomato (Fig. 4). Across the crops, filing activity is steadily on the rise indicating the scope of CRISPR across these species. Rice, maize and wheat lead the count in terms of patent focus. The patents originate predominantly from the US with the exception of rice where China holds the lead (Fig. 5).
Table 2 Lists the Selected Crops Against Their Value in 2018 (Source: USDA)
Fig. 4 Filing Trend for Selected Crops
Fig.5 Priority Country Distribution by Crop
Although developments in gene editing techniques are paving the way to crops of the future, many challenges still remain. Delivering gene editing tools into regenerative cells and non-transformable plants, increasing gene targeting efficiency, identifying new targets and pathways that can be manipulated, reducing off-target edits are some of the challenges that lie ahead. The application of plant gene editing tools is being gradually broadened from genetic research to crop breeding. However, the scale up of these techniques will present additional technical and regulatory challenges before they can have an impact on the market.
Recent Advancements in Battery Technology
Electric cars, wearables, smartphones, and other gadgets have seen rapid progress in the last few years. They are all commonly limited by one factor - power supplied by a battery. In this article we try to cover some recent developments in battery technology.
Advancements in battery technology have been incremental as a result of sustained research and slow development efforts. The last breakthrough was achieved in the early 1990s when lithium ion batteries were commercialized. Lithium batteries are expensive to manufacture, extremely sensitive to high temperatures, have a tendency to explode or catch fire if damaged, may require expensive on-board computers for battery management and pollute the environment. Despite the shortcomings, lithium ion batteries have prevailed, owing to lack of better alternatives and slow advancements in battery technology.
Car manufacturers are well aware of the battery problem. The development of better batteries has spurred technologies, such as electric vehicles, to become more commonplace. Broadly, engines in electric cars may be powered using large batteries charged from the grid or small batteries charged by fuel cells. Companies like Tesla have already scoffed at the idea of fuel cells for powering EVs. Tesla co-founder and CEO Elon Musk has gone so far as to call hydrogen fuel cells as “mind-bogglingly stupid,” and that they are a “load of rubbish”. On the other hand, Toyota and General Motors have invested in fuel cell technology.
Table 3 Lists Potential Battery Solutions and Advantages
One battery innovation in the foreseeable future is the development of liquid metal batteries. Liquid metal batteries are batteries in which all three active components (2 electrodes and molten solution) are in liquid form. As a result, the battery has low cost and longer lifespan. Liquid electrodes offer a robust alternative to solid electrodes, as they avoid common failure mechanisms of conventional batteries, such as electrode particle cracking. The all-liquid design avoids cycle-to-cycle capacity fade because the electrodes are reconstituted with each charge. Key players operating in the liquid metal battery market include Ambri Inc., EnerVault, Aquion, and Pellion Technologies.
Fig. 6: Ambri’s Liquid Metal Battery Explained
SILA Nanotechnologies, a company based in California, is working on a breakthrough lithium ion technology. The idea is to use microscopic silicon particles to store lithium inside their battery. The silicon anode in lithium silicon batteries enables storage of the same amount of energy in a smaller volume. These batteries perform up to 40% better and charge up to nine times as fast, due to the reduced thickness of the anode. SILA Nanotechnologies have partnered with major companies such as Samsung and Daimler. They are set to launch their products in 2019.
Fig. 7: (a) Sila anodes demonstrate excellent cycle life in matched full cells and <1%, cell level swelling over 400+ cycles (b) Sila’s technology is based on work published in 2010 Nature Materials (c) Sila’s stacked demo cell platform uses all commercial components and build methods paired with Sila’s proprietary anodes
On another front, research into aluminium ion batteries has begun and promises to be safer and cheaper than lithium ion batteries. In comparison to existing batteries, aluminium ion batteries can even have a hole drilled into them and still keep running. The cost of the battery in comparison is also cheaper, as aluminium is the third most abundant element on earth. Researchers at Stanford and the University of New South Wales feel that this is a promising technology, though still at an infancy stage in terms of development and commercial viability.
In conclusion, the high demand for batteries in electric vehicles, electronic devices, and utility storage creates a financial motivation that could foster the next wave of battery development. Advanced electric cars and battery utility storage will have a high potential for a viable large-scale market and leading market players would be keen to develop the best battery technology.