Universityof Toronto researcherSachdev Sidhuand his collaborators are engineering antibody molecules that can neutralize the novel coronavirus in the body before it invades cells.
Sidhu (left) already leads a differentteam that received supportin the first round of federal funding. The goal of that project is to design antiviral medicines that block viral replication.
With our two funded projects, we are working to develop molecules that can target the virus both inside human cells and on the outside to prevent it from getting in, says Sidhu, who is a professor of molecular genetics in the Faculty of Medicine.
Other teams in Canada, as well as in the U.K. and U.S., are looking to infuse Covid-19 survivors blood plasma containing antibodies into patientsto aid their recovery. Plasma transfusion, however, is fraught with challenges, including variability in efficacy between different donors and risk of disease transmission. Synthetic antibodies, on the other hand, represent a defined drug in terms of molecular content, efficacy and dosing regimen.
Rini has previously helped to determine how antibodies bind to and inactivate the SARS virus, the coronavirus that caused the outbreak in Asia more than 15 years ago. Also on the team isAlan Cochrane, a professor in the department of molecular genetics and an HIV virologist with expertise in viral RNA processing.
The antibodies will be engineered to block the so-called S-protein that forms spikes on the virus's surface. The spikes lock on to a protein called ACE2 on the surface of human cells to gain entry. Coating viral particles with synthetic antibodies should prevent the spikes from binding to ACE2.
Sidhu and Rini will also engineer antibodies that bind ACE2 to make it inaccessible to the virus. This type of engineered immunity surpasses the capacity of the bodys natural immune system since antibodies that react against self-proteins have been filtered out. If successful, the approach may obviate worries about viral mutations that can render drugs ineffective to new emerging viral strains becausethe host protein ACE2 does not change over time.
Sidhus team has advanced a technology called phage display to rapidly create and select human antibodies with desired biological properties, including blocking the virussspike protein. Over the last decade, his team has created hundreds of antibodies with therapeutic potential some of which are in clinical development through spin-off companiesand large pharmaceutical firms.
The group has demonstrated success with both approaches for inhibiting viral entry, having developed neutralizing antibodies that target the Ebola virus as well as antibodies that target the human host receptor of hantavirus or hepatitis C. Moreover, other research has shown that antibodies targeting SARS, a related virus whose genetic material is over 80 per cent identical to the one causing COVID-19, can clear infection in cells and mice.
Using phage display, in which tiny bacterial viruses called phages are instructed to create vast libraries of diverse antibodies, the team will select the antibodies that can kill the virus in human cells before testing them on mice and, eventually, patients. Experiments on mice could start within three to six months, Sidhu says.
In addition to creating antibodies tailored to the new virus from scratch, the researchers will also modify existing SARS-blocking antibodies so that they attack COVID-19 and provide an additional route to the development of a therapeutic.
Given the global spread of the virus, its possible that it will become endemic and circulate in the population like seasonal flu. And, like the flu, it could mutate into new strains that will evade acquired immunity and the vaccines that are being developed. By generating a panel of different antibodies, the researchers aim to stay one step ahead of the virus.
Our advances in antibody engineering technologiesand access to the complete genomes of the COVID-19 virus and its relatives provides us with an opportunity to create tailored therapeutic antibodies at a scale and speed that was not possible even a few years ago, says Sidhu.
Ultimately, we aim to optimize methods to the point where the evolution of new drugs will keep pace with the evolution of the virus itself, providing new and effective drugs in response to new outbreaks.
Originally posted here:
- June 11th At Westport, CT: Federal Red Flags, HIPAA Security Rules and Fraud Prevention - November 7th, 2009 [November 7th, 2009]
- Do not learn Dvorak! - November 7th, 2009 [November 7th, 2009]
- You Can’t Solve Problems By Making It Illegal To Have The Problem - November 7th, 2009 [November 7th, 2009]
- A Force Fix for Healthcare - November 7th, 2009 [November 7th, 2009]
- Yahble, HIT, Bubblecon, BIZDEV!, Solid State - November 7th, 2009 [November 7th, 2009]
- 15 things that suck about the Palm Pre - November 7th, 2009 [November 7th, 2009]
- What an Indie Genomics Lab Looks Like - November 7th, 2009 [November 7th, 2009]
- Practice Fusion: Class D Felony? - February 26th, 2010 [February 26th, 2010]
- Practice Fusion Responds - March 7th, 2010 [March 7th, 2010]
- Practice Fusion: Do the math: $44,000 is a LIE - March 10th, 2010 [March 10th, 2010]
- How Much Until Doctors Approve of 23andMe? - March 10th, 2010 [March 10th, 2010]
- Biochemicals as Media, Not Methods - March 10th, 2010 [March 10th, 2010]
- More Practice Fusion Reality Distortion - March 10th, 2010 [March 10th, 2010]
- Same Test Results: 23andMe is Myriad is BRCA is Medicine - March 12th, 2010 [March 12th, 2010]
- BRCA is 23andMe is Myriad is Medicine - March 13th, 2010 [March 13th, 2010]
- Getting Serious About Genomics as Common Medical Practice - March 15th, 2010 [March 15th, 2010]
- The New John Mackey of Genetics: Linda Avey? - March 15th, 2010 [March 15th, 2010]
- Keep the Medical, Well, Medical - March 16th, 2010 [March 16th, 2010]
- If 23andMe shuts down, it won’t be for some mundane reason like the bills weren’t paid - March 16th, 2010 [March 16th, 2010]
- If I Run A Medical Practice, How Do I Use A 23andMe? - March 17th, 2010 [March 17th, 2010]
- 23andMe Contract in Bad Faith - March 19th, 2010 [March 19th, 2010]
- Doctors CANNOT Use 23andMe Due To 23andMe’s Bad Faith Contract - March 20th, 2010 [March 20th, 2010]
- Pathway Compared to 23andMe and Navigenics - March 22nd, 2010 [March 22nd, 2010]
- There’s a Word for “Views Differ” When One View Is The State - March 24th, 2010 [March 24th, 2010]
- Association for Molecular Pathology, et al. v. USPTO, et al. – Opinion - March 29th, 2010 [March 29th, 2010]
- Birth of a Super Villain - April 3rd, 2010 [April 3rd, 2010]
- “Medical Products” like 23andMe must not become the new “Financial Products” - April 4th, 2010 [April 4th, 2010]
- How I Would Apply Genomic Technology In Clinical Use Today - April 5th, 2010 [April 5th, 2010]
- Gmail Enterprise: World’s Best EMR - April 6th, 2010 [April 6th, 2010]
- Brief Primer on Health Law Compliance - April 9th, 2010 [April 9th, 2010]
- Spoiler: You ARE the “Valids” - April 9th, 2010 [April 9th, 2010]
- Rachel Lehmann-Haupt Line by Line Take Down - April 9th, 2010 [April 9th, 2010]
- Is Medicare Bankrupt? What the Hell Is Going On? - April 17th, 2010 [April 17th, 2010]
- The Big Shuffle: Medicare Cuts Rates by 21.3% (but not “technically”) - April 17th, 2010 [April 17th, 2010]
- “Tech Hiring Binge” == “Fear for Your Job, Nerds” - April 18th, 2010 [April 18th, 2010]
- How Bad is Bad? $.20 on the Private Medical Insurance Dollar - April 20th, 2010 [April 20th, 2010]
- Update: How Bad is Bad? It Used to Be $.45 on the Medical Insurance Dollar - April 20th, 2010 [April 20th, 2010]
- World’s Best “EMR” for $1000: Google Spreadsheets + iPad - April 21st, 2010 [April 21st, 2010]
- Don’t Insult Me with your “AOL Keyword” Strategy, Google Health - April 21st, 2010 [April 21st, 2010]
- How to Play LAWGAMES - April 23rd, 2010 [April 23rd, 2010]
- Top 4 Predatory Schemes Encroaching on American Medicine: Part 1 - April 25th, 2010 [April 25th, 2010]
- What’s the Big Deal About iPads? - April 27th, 2010 [April 27th, 2010]
- Got Google Android for Google I/O - April 27th, 2010 [April 27th, 2010]
- Google Enterprise meets HIPAA and HITECH Compliant Laws - April 29th, 2010 [April 29th, 2010]
- Pixels of Accuracy CHALENGE: Diagnostic Medical Imaging - April 29th, 2010 [April 29th, 2010]
- 23andMe Launder AlioGenetics Doesn’t Even Bother to Remove 23andMe Logo - April 30th, 2010 [April 30th, 2010]
- Anthem of CT Denies $600 Until “Subscriber Responds to our Coordination of Benefits Questionnaire” - May 1st, 2010 [May 1st, 2010]
- Apple And Google Team Up To Launch Revolutionary Mobile Health System - May 1st, 2010 [May 1st, 2010]
- Funny Pictures from This Year Building the Medical Practice - May 6th, 2010 [May 6th, 2010]
- Remote Medical Video Monitoring on iPad and iPhone - May 7th, 2010 [May 7th, 2010]
- Google Calendar Overhead Waiting Room Display - May 7th, 2010 [May 7th, 2010]
- Various Whiteboards on Solid State Medical Operations - May 7th, 2010 [May 7th, 2010]
- The Raw Facts about Counsyl - May 7th, 2010 [May 7th, 2010]
- Brawndo: Still Mutilating Thirst, Still Not Yet Sold at the Stop-n-Shop Pharmacy - May 9th, 2010 [May 9th, 2010]
- Video: Google Enterprise to Outsource Medical Administration - May 9th, 2010 [May 9th, 2010]
- Gattaca: “The Matrix” of Genomics - May 11th, 2010 [May 11th, 2010]
- 23andMe Now Diagnoses Fatal Tay-Sachs Disease - May 12th, 2010 [May 12th, 2010]
- Why Was Pathway Targeted for FDA Enforcement and Not 23andMe? - May 15th, 2010 [May 15th, 2010]
- John Dolan on Aging and the Horrifying Conclusion of GWAS - May 16th, 2010 [May 16th, 2010]
- Sam R. Riley Wants To Tell You About Practice Fusion - May 17th, 2010 [May 17th, 2010]
- Response to “Genomic Medicine: Lost” - May 19th, 2010 [May 19th, 2010]
- Death And Taxes: CMS to IRS - May 19th, 2010 [May 19th, 2010]
- Please Stop Antagonizing the AMA - May 26th, 2010 [May 26th, 2010]
- Dan Vorhaus, Attorney At Law, Legally Advises Medical Doctors Can Use 23andMe To Provide Medical Advice - May 28th, 2010 [May 28th, 2010]
- Singularity Summit 2010 in San Francisco to Explore Intelligence Augmentation - June 7th, 2010 [June 7th, 2010]
- OpenPCR: DNA amplification for anyone - June 10th, 2010 [June 10th, 2010]
- FDA sends letters to 5 genetic testing companies - June 11th, 2010 [June 11th, 2010]
- Amazon And The NIH Team Up To Put Human Genome In The Cloud - March 31st, 2012 [March 31st, 2012]
- ReproSource Comments on New Study Linking Infertility to Genetics - April 25th, 2012 [April 25th, 2012]
- Genetics 101 Part 1: What are genes? - Video - April 30th, 2012 [April 30th, 2012]
- Red Ice Radio - David Icke - Hour 1 - The Manipulation of Humanity - Video - April 30th, 2012 [April 30th, 2012]
- Genetics Part 5: Human Genetic Disorders - Video - April 30th, 2012 [April 30th, 2012]
- C2CAM - The Nephilim, Genetic Manipulation - April 30th, 2012 [April 30th, 2012]
- Human Nature talk with Robert Sapolsky, Gabor Mate, James Gilligan, Richard Wilkinson - Video - April 30th, 2012 [April 30th, 2012]
- Human Genetic Diseases - Video - April 30th, 2012 [April 30th, 2012]
- Alien Scientist on Genetics, Implants - April 30th, 2012 [April 30th, 2012]
- Research and Markets: Genetics, 6th Edition International Student Version Continues To Educate Today's Students for ... - May 4th, 2012 [May 4th, 2012]
- Myriad Genetics to Present at the Bank of America Merrill Lynch 2012 Health Care Conference - May 4th, 2012 [May 4th, 2012]
- Genetics may explain some people's dislike of meat - May 4th, 2012 [May 4th, 2012]
- 'Blond Genes' May Vary Around the World - May 4th, 2012 [May 4th, 2012]