GOLLYGEE!

A group of researchers have developed a method for attaching drugs to the surfaces of red blood cells. RBC precursor cells are engineered to express a surface protein (purple oval) with a sortase substrate sequence. When the precursor cells become RBCs, sortase is added to form an RBC-enzyme intermediate. A modified drug can then react with the intermediate to form an RBC-drug conjugate. Picture from cen.acs.org

In this week’s CEN, Stu Borman describes a new drug delivery strategy. Researchers at The Whitehead Institute have developed a method for conjugating drugs to red blood cell surfaces increase drug longevity and bioavailability:

Hidde L. Ploegh, Harvey F. Lodish, and coworkers at MIT’s Whitehead Institute for Biomedical Research have created RBC-drug conjugates that could take drug longevity to another level (Proc. Natl. Acad. Sci. USA 2014, DOI: 10.1073/pnas.1409861111). They’ve shown longevities of 28 days in mice but hope for more in people, where RBCs live up to four months.

They engineer mouse or human RBC precursor cells to express a surface protein bearing a sequence recognized by the enzyme sortase. Once the cells develop into RBCs, they add sortase, forming a covalent RBC-enzyme intermediate. A modified drug can then react with the intermediate, expelling sortase and yielding an RBC-drug conjugate. Sortase-based cell-surface labeling is an established technique, but this is the first time it’s been used for diagnostic or therapeutic purposes.

An oil rig.

Eric Hand reports on a new study in Science Magazine that attempts to correlate an increase in seismic activity in Oklahoma to the hydraulic fracturing boom there. Oklahoma has had more magnitude 3 earthquakes this year than California. In the process of extracting natural gas, large amounts of water are pumped or stored underground. The pressure that is built up is thought to weaken the forces keeping a fault locked, and potentially trigger a rupture. The study by Katie Keranen suggest that the pressure build up could trigger seismic activity as far as 35 km away, and could one day threaten Oklahoma City:

The vast majority of Oklahoma’s more than 9000 injection wells cause no trouble whatsoever. Not so with four high-volume disposal wells used in a dewatering operation near Oklahoma City, the study suggests. The wells pump more than 4 million barrels (477,000 cubic meters) of water into the ground every month. Katie Keranen, a geophysicist at Cornell University, and colleagues found that the four wells are capable of triggering the earthquakes. By combining precise maps of Jones swarm earthquakes with a hydrogeologic model, they showed that an expanding underground wave of pressure from the wells (named Chambers, Flower Power, Deep Throat, and Sweetheart) closely matched the places and times of the quakes in the swarm. The company that owns the wells, New Dominion, based in Tulsa, Oklahoma, declined to answer questions about the study and released a statement saying that it was based on “false assumptions.”

Keranen is concerned that the four disposal wells lie close to the Nemaha fault, which runs through Oklahoma City and is large enough to host a devastating magnitude-7 earthquake. The main fault is unlikely to rupture because local stresses push its two sides together, Keranen says, but an unmapped offshoot might be more susceptible to rising water pressures. In the long term, a magnitude-6 earthquake near Oklahoma City is a plausible hazard, she says.

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drug delivery via red blood cells

is fracking causing an increase in earthquakes?

happy fourth of july!