America and China in the Industry

The United States is the most influential player in the global biotech market, with 108 billion dollars in revenue, a market capitalization of 890 billion dollars, and four of the five largest biotech companies in the world. The Bay Area is the metro area with the highest concentration of the industry in the world.

Source: https://www.statista.com/topics/1634/biotechnology-industry/

Meanwhile, in China, of the 42 cancer drugs that have been approved globally, only four are available in China. This despite the fact that China is the second largest pharmaceutical market after the United States. Nevertheless, growth is evident. Over the past decade or so, government support for biomedical companies has increased, with the administration including the industry as a plank in many recent five-year plans and stipulating that the sector should exceed 4% of GDP by 2020. China also has over a hundred life-science parks, locally run havens of tax breaks and subsidies that have helped lure talent, both academic and business-oriented. A large part of this human capital comes from people born in China but with extensive academic or work histories in North America. Since the financial crisis, domestic investment has shifted towards the small but clearly growing industry away from the bloated manufacturing and real estate sectors, especially as awareness of China’s lag in drug availability and ageing population has grown.

Job growth in the Chinese biomedical industry is increasingly being driven by Chinese start-ups, some of which may even be headed by expatriates. The domestication of the industry, driven by the skyrocketing amount of funds raised by Chinese venture capital firms, parallels the new wave of research being undertaken by domestic universities, complete with plentiful grant money. Some experts even characterize Chinese grants as being more willing to support high-risk research projects compared to their American counterparts.

Source: https://www.nature.com/articles/d41586-018-00542-3

An aging population, limited water supplies, and polluted land are all recognized incentives for China to invest in agriculture biotechnology. However, China is more competitive in the gene-editing market, especially via investments in American businesses that, because they are mostly startups, do not have their foreign investments monitored for potential threats to national security by the Committee for Foreign Investment in the United States (CFIUS).

The hot peace with China perhaps raises fears that tight regulation puts America at risk of losing technology races and thereby compromises national security. It’s long been accepted as conventional wisdom that American innovation and global competitiveness are hampered by a strict regulatory regime, the type of system that, for instance, has been encouraging many American-based researchers to file CRISPR patents in China in the last few years. American regulations involve more than just a national security calculus, of course, and also manage the nation’s health and safety. So while on the one hand it is true that American regulators don’t tend to accept riskier or more ambitious proposals at the rate that a lot of other countries do, on the other this narrative fits neatly into a neoliberal derision for government interference in markets that’s dominated our policymaking for decades. 

Source: https://worldview.stratfor.com/article/biotechnology-biotech-china-united-states-crispr-genome-agriculture-trade-war

 

 

Biosensors Today

 

Biomedical Sensors constituted an estimated $9.554 billion dollar market in 2017 that is projected to reach $11.912 billion by 2023. Here is a Table of Top Company Innovators in the Biomedical Sensors Market.

Sources:

For the evaluations: https://www.prnewswire.com/news-releases/biomedical-sensors-market-2023-300658111.html

For the table: https://www.businesswire.com/news/home/20160222006403/en/Biomedical-Sensors-Market-Report-2016—2015-2020

This article summarizes some of the innovations in contact lens biosensors: https://spectrum.ieee.org/biomedical/devices/smart-contact-lenses-and-eye-implants-will-give-doctors-medical-insights

“Google, through its biology offshoot, now named Verily Life Sciences, and the Swiss pharmaceutical giant Novartis International, through its eye care division Alcon, joined forces to design, develop, and commercialize smart contact lenses for diabetics. If the project reaches its goals, these lenses will spare diabetics from the daily finger pricks typically used to measure blood glucose levels, instead employing embedded microelectronics to measure glucose in the wearer’s tears.”

“Our glaucoma lens directly measures IOP using piezoresistive strain sensors; these sensors contain electrical conductors that stretch under pressure, thus changing their resistance and providing a readout of IOP.”

“Many types of sensors have been developed for measuring the glucose in these tears. The best known is the electrochemical sensor devised by Babak Parviz while he was an electrical engineering professor at the University of Washington; he later became a director at Google and launched the Verily-Alcon smart-lens project. This sensor uses an enzyme that catalyzes glucose to create hydrogen peroxide, which is further oxidized at the electrode to release electrons, thus generating an electrical current proportional to the glucose concentration.”

“Other types of sensors use fluorescent or colloidal-crystal particles to provide an optical readout that indicates the amount of glucose present. For example, users could look in the mirror to check the color of tiny dots on their smart lenses.”

 

 

 

 

Novartis

The particular identification and directing of molecular therapies to cancerous cells is an optimal treatment strategy, shown to better address, contain, and/or avoid any toxicity (Madaan et al., 2014). Here, we will focus on cancer drug delivery via folic acid receptors. The overexpression of these receptors in epithelial cancer cells was discovered and used as a method of drug delivery. This method was then improved by the introduction of a dendrimer scaffold, serving as a prime example of how biomolecular engineering capitalizes on existing biological systems. Folic acid is attracted to the folate receptor, whose protein is often overexpressed up to one hundred-fold in epithelial (referring to tissue linings in organs and blood vessels) cancer cells (like those involved in breast, lung, and brain cancers), and folic acid and folate receptors form folic acid complexes. Many folic acid complexes are proficient in molecular targeting to tumors (Zhang et al., 2010). These folate receptor proteins are expressed on the regions of cells facing interstitial tissue, rather than on the interior-facing surfaces where normal expression takes place. It is precisely this proximity to blood that allows folic acid, when active as a tracking vessel, to have an astute, biomedically conducive awareness of the particularities of cancer cells (Zhang et al., 2010). Folic acid is minuscule enough to easily find its way inside tumors and is hardly expensive, so it has experienced broad popularity in biochemical recognitions and analysis and in biological tracking (Mishra et al., 2011). Protein-based toxins, liposomes enveloped in drugs, and many types of nanoparticles are some common targets of folic acid (Mishra et al., 2011).

One complication of targeting mechanisms predicated on folate molecules by themselves is that they have levels of affinity constrained by folate quantity (many are needed for adequate affinity). In more problematic scenarios, the circumscribed attraction of folate targeting materials even bounded the outputs of drug delivery to an extent dreadfully inadequate for cancer cell therapeutics (Majoros, Myc, Thomas, Mehta, & Baker, 2006).

Biomolecular engineers sought to improve this system of drug delivery by incorporating dendrimers into the system. Experimental analysis of a drug delivery device based on a polyamidoamine scaffold, branched to multiple folic acid molecules, within in vivo contexts, has made apparent the advantages of this nanostructured device transporting drugs as opposed to the folic acid molecules themselves operating individually and freely (Madaan et al., 2014). The most plausible reason for folate acid molecules working through the scaffold being more effective than those operating independently is the multiplicity and high level of attraction of the interplay taking place across the folic acid groups externally on the dendrimer (Patri, Majoros, & Baker, 2002). Dendrimer scaffolds branched to folic acid molecules were quantitatively tested in response and resulted in a strength of ligand-protein (in this case, surface folate binding proteins) binding (important for efficiency and continuity in therapeutic drug delivery) in the weakest regions of at least 2,000 times as strong as individual folic acid molecules (Kang, 2011).

Collections of such experimental data vindicate the capacity of polyamidoamine dendrimer scaffolds to function in multivalent binding systems. Quantitatively, there was a positive, linear relationship between the association constant (representing binding strength) and the number of targeting vessels involved (demonstrating its value as an explanatory variable) (Patri et al., 2002). In other words, the more the polyamidoamine dendrimers are branched, the more targeting molecules (in this case, folic acid) they contain, and the higher the affinity between the ligand and the receptor. In this way, the targeting and tracking mechanism is streamlined.

Polyamidoamine dendrimers are key to the development of expansive, multipurpose cancer-therapy nanostructured devices. It is important, then, that there are several modifications that can improve the effectiveness of these dendrimers. Adding a partial acetyl group to the dendrimer allows for the neutralization and containment of some of the negative effects caused by amino groups comprising the dendrimer. Such a measure also increases solubility (important for binding), and prevents unintended, overly broad and promiscuous detection and targeting over the course of drug transport (Majoros et al., 2006). Amino groupings without the added acetyl group can still be helpful in combining folic acid (again, important because it targets the folate receptor proteins), drugs like methotrexate, and contrast agents needed for clear imaging (Majoros et al., 2006).

Methotrexate, a drug commonly conjugated to folic acid (which has long been suspected of being able to neutralize some of the harmful side effects of methotrexate, as a “folate antagonist”) is a chemotherapeutic drug often applied to forms of cancer (Thomas et al., 2005) and arthritis (Weinblatt, 2013). The DNA replication of cancerous cells that enables the overexpression of folate receptors relies on the dihydrofolate reductase enzyme, which is blocked by methotrexate. Folic acid binds to these overexpressed receptors, and the dendrimer delivers methotrexate to those cells. It is in this way that the overexpressed receptor-expressing cancer cells are killed (Zhang et al., 2010). Thereby, the folic acid-methotrexate device is adept in accurately tracking and degrading these cancer cells through their relationship with excessively expressed, yet fully-formed, folate receptor proteins (Quintana et al., 2002).

Here, Quintana et al. summarize their work on the folic acid receptor drug delivery system:

The cellular uptake and cytotoxicity of an engineered multifunctional dendritic nanodevice containing folic acid (FA) as the targeting molecule, methotrexate (MTX) as the chemotherapeutic drug, and fluorescein (FI) as the detecting agent were studied in vitro.
Methods: The device is based on an ethylenediamine core polyamidoamine dendrimer of generation 5. Folic acid, fluorescein, and methotrexate were covalently attached to the surface to provide targeting, imaging, and intracellular drug delivery capabilities. Molecular modeling determined the optimal dendrimer surface modification for the function of the device and suggested a surface modification that improved targeting. Results: Three nanodevices were synthesized. Experimental targeting data in KB cells [a tumor cell] confirmed the modeling predictions of specific and highly selective binding. Targeted delivery improved the cytotoxic response of the cells to methotrexate 100-fold over free drug.
Conclusions: These results demonstrate the ability to design and produce polymer- based nanodevices for the intracellular targeting of drugs, imaging agents, and other materials (Quintana et al., 2002)

This multifunctional dendrimer-based device can be abbreviated as G5-FI-FA-MTX. The G5-FI-FA-MTX conjugated product activated molecular pathways that lead to the inhibition of cell growth in KB tumor cells, because the capacity of G5-FI-FA-MTX nanodevices to detect, target, and finally repress the proliferation of cancerous cells directly derive from their folic acid component’s affinity to overexpressed folate receptor proteins (Zhang et al., 2010).

Drugs primarily useful for cancer therapy traditionally are dangerous due to a lack of precision in toxicity. However, precise polymer-predicated targeting techniques tailored to cancer cells can bridge many of these biomolecular inadequacies (Madaan et al., 2014).

When fabricated to completion, these nanodevices are deeply effective, transporting chemotherapeutic drugs to specifically selected cancer cells. Manufacturing these devices at larger material scales and ensuring real-life clinical familiarity should follow.

Dendrimers are nanostructures, and drug delivery often encompasses the conceptual space of nanoengineering. A dexterity in working with transport systems inside of cells as well as with imaging methodologies for mapping the cellular uptake of the given transported biomaterials would allow nanodevices to carry out multi-purposed processes.

Polymers can be structurally altered in order to integrate biomaterials applicable to targeting endeavors. Sending the polymer directly to the tumor brings therapeutic drugs with the facility to destroy the tumor cells. As these combinations of polymers and cancer therapy drugs are made more accurate and specific in tracking cancerous cells and become embedded in more complex systems of device manufacture, toxicity is minimized and the most restorative characteristics of the drugs are highlighted (Madaan et al., 2014).

Polymeric drug conjugates have several advantages over free drugs, especially since they face decreased drug resistance (Patri et al., 2002). Several synthetic and natural polymers of this sort have been tested in the past decade for targeting tumor cells (Kang, 2011).

Ideally, drug delivery mechanisms specifically geared for tumor cells necessitate an apparatus advanced enough to contain a variety of functionally central parts, like therapeutic drugs and fluorescent sensors (Majoros et al., 2006). Polyamidoamine dendrimers can build such transport systems because of their well-defined branches, themselves containing (either within interior void space or by covalent bonding on their surface) a plethora of biomolecules (Zhang et al., 2010). And thinking beyond these particular tactics for drug delivery, dendrimers have been utilized for their carrying qualities in a wide spectrum of medical capacities, whether they are agents for delivering drugs, sharpening imaging, or outlining radioactive molecules (Abbasi et al., 2014).