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© 2011, 2012 Health Futures Digest
| We reported last month on nano-engineered “zinc fingers”, amino acid protuberances that emanate from a single zinc ion that automatically bind to miscoded strands of DNA, stimulating the body’s innate repair mechanism to recode the gene correctly, thereby fixing whatever problem the bad gene was causing, without harmful side effects. If you think about it, this is enormously significant. It seems likely that the long-promised payoff of gene therapy is about to be delivered. Wired Magazine seems to think so too, and has carried two further interesting descriptions of the research, which we summarize here.
Gene therapy and nanotechnology have also been brought together in the form of gene-nanoparticle complexes to activate brain stem cells in mice, in hopes such therapy might one day be able to repair brain damage. Alert to the exciting potential of nanomedicine, the US National Institutes of Health are funding research into nanomedical solutions to pulmonary and vascular problems. Evidence of that potential is visible in a nanoscale double bombshell loaded with chemotherapy and anti-angiogenic drugs that has destroyed tumors in animals, while sparing healthy tissue, and in a nanoemulsion to treat cold sores that has passed Phase II clinical trials and is headed for Phase III. The technology is also being adapted to other forms of herpes, and vaginitis. Other nanomedical news:
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| Gene Therapy Breakthrough
“Using a package of synthesized zinc fingers, cells can be tricked into doing nano-surgery on their own genes,” reports Wired. “The zinc fingers home in like a guided missile on the exact spot in the genome doctors are trying to target and then bind to it. DNA-devouring enzymes then cut through the double helix of DNA at the exact beginning and end of the targeted gene, and a template of donor DNA helps rebuild the deleted strand.” The technique has been successfully applied in vitro by researchers at Sangamo BioSciences in California, to T-cells extracted from a SCID (Severe Combined Immunodeficiency Disease — Bubble Boy disease) patient. The defective gene was corrected in 18 percent of the cells, which should be more than enough to cure the disease, since “it only takes one corrected T-cell to repopulate a person’s immune system with healthy cells,” as Wired reports it. The first clinical trials will probably involve SCID patients, but the technology can be applied to a host of human diseases. University at Buffalo scientists have delivered genes into the brains of living mice via customized nanoparticles, with no apparent toxic effect. The gene-nanoparticle complexes were used to activate brain stem cells (also called progenitor cells) in vivo, which opens up the possibility of directing these otherwise idle cells to replace cells destroyed by trauma, stroke, or neurodegenerative diseases such as Parkinson’s. Furthermore, the nanoparticles could be useful for studying the genetics of brain disease (aided by tools such CellviZio, an in vivo imaging technology enabling brain cells to be observed as they express genes, without harming the animal), and may be less risky as well as cheaper and faster to produce than the engineered viruses currently used to deliver genetic payload to cells. The nanoparticles are made from hybrid, organically modified silica (ORMOSIL), and can be tailored to target gene therapies for specific tissues and cell types. With a US$12.5 million grant awarded by the National Institutes of Health, over the next five years a team of scientists from several US universities will develop nanoscale agents to provide early diagnosis and treatment of acute pulmonary and systemic vascular injury. Specifically, the team will be developing a way to trigger a breakdown of targeted nanoparticles after they deliver their drug or antiviral payload to arteries under stress or diseased. By attaching folic acid molecules to nanoparticles, University of Michigan researchers have found a way to deliver chemotherapeutic cancer drugs without the toxic side effects of conventional delivery methods. Cancer cells readily internalize the folic acid molecules — along with their deadly payload. The therapy has worked in animals, and human clinical trials are anticipated within 18 months. MIT researchers have also combined cancer biology, pharmacology, and engineering to create a dual-chamber, double-acting “nanocell” that has worked against melanoma and Lewis lung cancer in mice. Their technology not only delivers chemotherapy but also an anti-angiogenesis drug to destroy the tumor’s blood supply. The nanocell is “a balloon within a balloon.” The outer balloon holds the anti-angiogenic drug and the inner balloon the chemotherapy drug. Once inside the tumor, the outer balloon bursts, deploying the anti-angiogenic drug and destroying the blood vessels feeding the tumor. The inner balloon then slowly releases the chemotherapy. Eighty percent of mice receiving the nanocell treatment survived beyond 65 days, versus 30 days for mice treated with the best available conventional therapy and 20 days for untreated mice. The nanocell worked better against melanoma than lung cancer, indicating the need to tweak the design for different cancers. NanoBio Corporation has successfully completed a Phase 2 study of a topical “nanoemulsion” called NB-001 in patients with herpes labialis (cold sores). Phase 3 trials will be held next year. NB-001 is comprised of nanoscale water/oil droplets coated with a potent anti-viral, anti-bacterial and anti-fungal surfactant. The particles accelerate the healing of skin ulcers by killing the herpes viruses at the lesion site. Patients who received the highest dose of NB-001 (0.1%) trended to show healing one day sooner than subjects in the control group. A significant proportion of subjects on the highest dose of NB-001 had healing two or more days earlier than the control group. There were no drug-related adverse events, reports of drug-induced skin irritation or drop-outs due to adverse events. The nanoemulsion technology platform could be used to treat other topical infectious diseases. In fact, clinical trials of a proposed treatment for nail fungus (onychomycosis) are already planned for 2006, and other products in the pipeline include treatments for genital herpes, shingles, and vaginitis. The strength, flexibility and light weight of carbon nanotubes may lead to improved flexibility and strength of artificial bone, new types of bone grafts, and better treatments for osteoporosis. The polymers, peptide fibers, and other materials currently used to make artificial bone scaffolds are relatively weak and are sometimes rejected by the body. UC Riverside researchers have demonstrated that carbon nanotubes can mimic the role of collagen as a scaffold for inducing the growth of hydroxyapatite crystals. A team of US and Japanese researchers is working on a sheath of platinum nanowires that would be fed via catheter through the circulatory system to the brain or any other part of the body. The individual nanowires would branch out into vanishingly small blood vessels until they reached specific locations to report on the electrical activity of a single nerve cell, or small groups of nerve cells. They would not impede blood flow or the exchange of materials through the blood-vessel walls. The team has already conducted a proof-of-principle experiment in vitro, successfully detecting the activity of individual neurons lying adjacent to the blood vessels in a tissue sample. If the technique works in vivo, it would make today’s positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scans look fuzzy and crude in comparison, and should lead to a whole new understanding of neurological diseases and much better diagnosis and treatment. The nanowires promise not only to pinpoint damage from injury and stroke, localize the cause of seizures, and detect the presence of tumors and other brain abnormalities, but also to treat Parkinson’s and similar diseases by delivering electrical impulses. Parkinson’s patients who do not respond to medication are already commonly treated by inserting wires through the skull and into the brain, a process that can cause scarring of the brain tissue. The nanocatheter approach would eliminate the side effects and be much more accurate. The platinum nanowires may be replaced by electroactive polymer nanowires, which would not only conduct electrical impulses but also change shape in response to electric fields, allowing the nanowires to be steered through the brain’s circulatory system. They would also be 20 to 30 times smaller, biodegradable, and suitable for short-term brain implants. Nanoporous Adsorbents; Nanovalve Nanoporous adsorbents — sponges with pores only nanometers in diameter — could be used to soak up and store hydrogen for fuel cells, malodorous gases in pet litter, and toxins in the environment. Nanopores increase the surface area of the sponge — as much as five football fields in one gram of material — so the material absorbs more. Nanoporous adsorbents are also likely to be popular in oil refineries, as high surface area catalysts, and in biomedicine and biochemistry, to separate out complex fluids and carry out complex catalytic reactions. One available nanoporous adsorbent soaks up air and thus provides thermal insulation. The company that makes it has also developed a cooler with seven times the cooling power of ice. It works by evaporating water from nanoporous adsorbents, and could provide low weight. low cost cooling on demand for shipping (for example) drugs. In another interesting development, UCLA chemists have created a “nano valve” that can trap and release molecules on demand. It has potential use as a drug delivery system. The valve’s moving parts — switchable rotaxane molecules — are attached to a 500 nanometer-wide piece of porous silica glass whose pores, only a few nanometers in diameter, are big enough to let target molecules in and out but not big enough for the switchable rotaxane molecules. Chemical energy supplies a single electron as the power supply to move the rotaxane over (or away from) a pore opening. Nanoparticles known as quantum dots (“Qdots”) can fluoresce much more brightly than a dye molecule, giving them great potential in biological imaging, sensors, and DNA chips to name just a few applications. But Qdots are expensive to manufacture, and since they contain heavy metals and are chemically reactive they must be encased in polymer for use as biological markers, adding to the cost. Even then, the metals can leach through the polymer. Cornell University researchers have created a benign and inexpensive equivalent to Qdots they call “CU dots,” which are made by surrounding fluorescent dyes with a silica shell. CU dots are relatively inert and the silica shell — basically glass — is easy to make using conventional silicon manufacturing technology. Both Qdots and CU dots are 20-30 times brighter than single dye molecules in solution and retain their fluorescence longer. CU dots can be made with a wide variety of dyes, producing a large assortment of colors. The researchers successfully tested their dots as biological markers by attaching an immunoglobin E antibody and observing as the dot/antibody combination attached to leukemia mast cell receptors. Chinese scientists have discovered that the addition of gold nanoparticles to the polymerase chain reaction (PCR) process (a method of duplicating DNA to produce enough material for genetic testing) reduces the incidence of errors during the copying process. PCR is indispensable in modern forensics and genetic research and diagnosis. |
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