Scientists have demonstrated a new way to precisely target cells by distinguishing them from neighboring cells that look quite similar.
Even cells that become cancerous may differ from their healthy neighbors in only a few subtle ways. A central challenge in the treatment of cancer and many other diseases is being able to spot the right cells while sparing all others.
In a paper published 20 August inScience FirstReleasea team of researchers at the University of Washington School of Medicine and theFred Hutchinson Cancer Research Centerin Seattle describe the design of new nanoscale devices made of synthetic proteins. These target a therapeutic agent only to cells with specific, predetermined combinations of cell surface markers.
Remarkably, these 'molecular computers' operate all on their own and can search out the cells that they were programmed to find.
"We were trying to solve a key problem in medicine, which is how to target specific cells in a complex environment," said Marc Lajoie, a lead author of the study and recent postdoctoral scholar at the UW MedicineInstitute for Protein Design. "Unfortunately, most cells lack a single surface marker that is unique to just them. So, to improve cell targeting, we created a way to direct almost any biological function to any cell by going after combinations of cell surface markers."
The tool they created is called Co-LOCKR, or Colocalization-dependant Latching Orthogonal Cage/Key pRoteins. It consists of multiple synthetic proteins that, when separated, do nothing. But when the pieces come together on the surface of a targeted cell, they change shape, thereby activating a sort of molecular beacon.
The presence of these beacons on a cell surface can guide a predetermined biological activity -- like cell killing -- to a specific, targeted cell.
The researchers demonstrated that Co-LOCKR can focus the cell-killing activity of CAR T cells. In the lab, they mixed Co-LOCKR proteins, CAR T cells, and a soup of potential target cells. Some of these had just one marker, others had two or three. Only the cells with the predetermined marker combination were killed by the T cells. If a cell also had a predetermined "healthy marker," then that cell was spared.
"T cells are extremely efficient killers, so the fact that we can limit their activity on cells with the wrong combination of antigens yet still rapidly eliminate cells with the correct combination is game-changing," said Alexander Salter, another lead author of the study and an M.D./Ph.D. student in the medical scientist program at the UW School of Medicine. He is training in Stanley Riddell's lab at the Fred Hutchinson Cancer Research Center.
This cell-targeting strategy relies entirely on proteins. This approach sets it apart from most other methods that rely on engineered cells and operate on slower timescales.
"We believe Co-LOCKR will be useful in many areas where precise cell targeting is needed, including immunotherapy and gene therapy," said David Baker, professor of biochemistry at the UW School of Medicine and director of the Institute for Protein Design.
Theresearch was conducted at the Institute for Protein Design, the Immunotherapy Integrated Research Center at the Fred Hutchinson Cancer Research Center, and the UW Department of Bioengineering.
The co-lead authors of this work are Marc J. Lajoie (supported by a Washington Research Foundation Innovation Postdoctoral Fellowship and a Cancer Research Institute Irvington Fellowship from the Cancer Research Institute), Scott E. Boyken (supported by the Burroughs Wellcome Fund Career Award at the Scientific Interface), and Alexander I. Salter (supported by the Hearst Foundation and Fred Hutchinson Cancer Research Center Interdisciplinary Training Grant in Cancer Research).
This work was also supported by the National Institutes of Health, National Science Foundation, the Defense Threat Reduction Agency, Nordstrom Barrier Institute for Protein Design Directors Fund, Hearst Foundation, Washington Research Foundation and Translational Research Fund, Howard Hughes Medical Institute, Open Philanthropy Project, and The Audacious Project organized by TED.
Several authors are inventors on patents related to this work. Some hold equity in Lyell Immunopharma. Some authors are now employees or consultants of Lyell Immunopharma.
This news release was written by Ian Haydon of the Institute for Protein Design.
Read the original:
New 'molecular computers' find the right cells - UW Medicine Newsroom
- Is there an alternative to radiation - November 8th, 2009 [November 8th, 2009]
- Taiwan exploring how nanotech affects health - November 8th, 2009 [November 8th, 2009]
- A new way of treating cancer on the way? - November 8th, 2009 [November 8th, 2009]
- Lasers can destroy cancer cells - November 8th, 2009 [November 8th, 2009]
- Fluorescent molecules can be biomarkers - November 8th, 2009 [November 8th, 2009]
- Quick blood tests by using a nanodevice - November 8th, 2009 [November 8th, 2009]
- Where will medicine be 20 years from now - November 8th, 2009 [November 8th, 2009]
- History of nanotechnology - November 8th, 2009 [November 8th, 2009]
- Nanotech and Cancer - November 8th, 2009 [November 8th, 2009]
- Nanotechnology in medicine - November 8th, 2009 [November 8th, 2009]
- How does cancer start - January 25th, 2010 [January 25th, 2010]
- Lung cancer symptoms - January 26th, 2010 [January 26th, 2010]
- Signs of breast cancer - January 27th, 2010 [January 27th, 2010]
- Famous people with cancer - January 29th, 2010 [January 29th, 2010]
- Metastatic renal cancer - January 30th, 2010 [January 30th, 2010]
- What causes skin cancer - January 31st, 2010 [January 31st, 2010]
- How many people die from cancer each year - February 1st, 2010 [February 1st, 2010]
- How much money is spent on cancer research - February 2nd, 2010 [February 2nd, 2010]
- Colon cancer warning signs - February 4th, 2010 [February 4th, 2010]
- Prostate cancer symptoms - February 4th, 2010 [February 4th, 2010]
- Nano-devices that cross blood-brain barrier open door to treatment of cerebral palsy - April 25th, 2012 [April 25th, 2012]
- Nano-devices that cross blood-brain barrier open door to treatment of cerebral palsy, other neurologic disorders - April 25th, 2012 [April 25th, 2012]
- Nanomaterial properties in complement activation: lessons from nanomedicine - Video - May 4th, 2012 [May 4th, 2012]
- OMICS Group :: International Conference and Exhibition on Nanotechnology - May 4th, 2012 [May 4th, 2012]
- Use of Nanotechnology in Medicine [FOX 11-27-2011] - Video - May 4th, 2012 [May 4th, 2012]
- Cancer Nanomedicine - Detection - Video - May 4th, 2012 [May 4th, 2012]
- Cancer Nanomedicine - Video - May 4th, 2012 [May 4th, 2012]
- HBIO Reports First Quarter 2012 Revenue Growth of 8% Over First Quarter 2011 - May 5th, 2012 [May 5th, 2012]
- Nano science, focus of Education Ministry - May 7th, 2012 [May 7th, 2012]
- Drug-resistant Bacteria - Designing Nanoparticles For High Antibiotic Doses - May 7th, 2012 [May 7th, 2012]
- Research and Markets: Global Market for Nano Silver - May 10th, 2012 [May 10th, 2012]
- Cracking study makes nanotech breakthrough - May 10th, 2012 [May 10th, 2012]
- Nanoparticles may pose environmental threat - May 16th, 2012 [May 16th, 2012]
- Global Nanobiotechnology Industry - May 17th, 2012 [May 17th, 2012]
- 'Inability to give back Singur land my biggest regret' - May 20th, 2012 [May 20th, 2012]
- 'KOREA PACK 2012' for Packing process industry to be held at KINTEX - May 23rd, 2012 [May 23rd, 2012]
- New ISO Technical Report Guides Characterization of Nanomaterials in Toxicology - May 29th, 2012 [May 29th, 2012]
- DNA strands create tiniest Smileys - May 30th, 2012 [May 30th, 2012]
- Health and fitness agenda: Evolution Asia Yoga Conference - June 2nd, 2012 [June 2nd, 2012]
- UC Davis work in humanities receives $150,000 in UC-wide grants - June 2nd, 2012 [June 2nd, 2012]
- Computer-designed proteins 'may help fight variety of flu viruses' - June 3rd, 2012 [June 3rd, 2012]
- 'Nano technology' [program can pay off big for IRSC students - June 3rd, 2012 [June 3rd, 2012]
- Computer-designed proteins programmed to disarm variety of flu viruses - June 3rd, 2012 [June 3rd, 2012]
- Jugaad innovators don't plan - they improvise - June 6th, 2012 [June 6th, 2012]
- Health and fitness agenda: World Blood Donor Day - June 9th, 2012 [June 9th, 2012]
- OMICS Group :: Journal of Nanomedicine - June 9th, 2012 [June 9th, 2012]
- Researchers develop a 'time bomb' to fight cardiovascular disease - June 10th, 2012 [June 10th, 2012]
- Nanotechnologists develop a 'time bomb' to fight cardiovascular disease - June 10th, 2012 [June 10th, 2012]
- 'Time bomb' to fight cardiovascular disease developed - June 11th, 2012 [June 11th, 2012]
- Asia's First Graphene Nano-Tech Facility Opens In Singapore - June 13th, 2012 [June 13th, 2012]
- How worms are pioneering remote control medicine - June 13th, 2012 [June 13th, 2012]
- Golden Helix Establishes Direct Presence in Japan - June 13th, 2012 [June 13th, 2012]
- STDs Blocked by Nano Gel, Study Suggests - June 15th, 2012 [June 15th, 2012]
- Real Products, Different Results - June 15th, 2012 [June 15th, 2012]
- The Puridone Program - A Breakthrough for Painkiller Addiction - June 15th, 2012 [June 15th, 2012]
- Six startup medical device firms compete in Memphis for fame and fortune - June 19th, 2012 [June 19th, 2012]
- International Nanomedicine Conference bound for Sydney: July 2-4, 2012 - June 19th, 2012 [June 19th, 2012]
- Taming light with graphene - June 21st, 2012 [June 21st, 2012]
- Today on New Scientist: 25 June 2012 - June 26th, 2012 [June 26th, 2012]
- A step towards the future - July 1st, 2012 [July 1st, 2012]
- Genia Technologies Collaborates with Professors Jingyue Ju at Columbia and George Church at Harvard to Develop a ... - October 4th, 2012 [October 4th, 2012]
- Scientists Invited To Submit Proposals For Biological Research In Space - October 4th, 2012 [October 4th, 2012]
- Research and Markets: Micro-Nano Technology XIII from the 13th Annual Conference of Chinese Society of Micro-Nano ... - October 6th, 2012 [October 6th, 2012]
- $80M research facility to open at UMass Lowell - October 6th, 2012 [October 6th, 2012]
- Nano-revolution in drugs delivery - October 8th, 2012 [October 8th, 2012]
- SENAI/SESI of Sao Paulo Selects NanoProfessor as Foundation for "Nanomundo" Nanotechnology Education Initiative - October 8th, 2012 [October 8th, 2012]
- Delivering an integral approach to emotional and mental health - October 9th, 2012 [October 9th, 2012]
- NanoGuardian's On-Dose NanoEncryption Brand Protection Technology to Be Presented at AAPS Annual Meeting - October 11th, 2012 [October 11th, 2012]
- Il Nano Mondo del professor Ennio Tasciotti - Video - October 30th, 2012 [October 30th, 2012]
- Deakin University - Practical Science - Nano medicine - Video - October 30th, 2012 [October 30th, 2012]
- 2012 Deakin University 3 Minute Thesis Finalist - Jarrad Altimari - Video - October 30th, 2012 [October 30th, 2012]
- Nano Medicine from "Development of Nanotechnology in Hong Kong" - Video - October 30th, 2012 [October 30th, 2012]
- NANO Medicine 1 3 xvid - Video - October 30th, 2012 [October 30th, 2012]
- Nanolääke // Nano medicine - Video - October 30th, 2012 [October 30th, 2012]
- NANO Medicine (1-3) - Video - October 30th, 2012 [October 30th, 2012]
- Jefferson County, Colorado's Bioscience Industry - Video - October 30th, 2012 [October 30th, 2012]
- NanoMission - Nanomedicine NanoBot - Video - October 30th, 2012 [October 30th, 2012]
- Study aims to unlock mysteries of autism - November 20th, 2012 [November 20th, 2012]
- Catherine Griwkowsky - November 22nd, 2012 [November 22nd, 2012]
- Kulkarni to be feted at Bangalore Nano 2012 - November 26th, 2012 [November 26th, 2012]