Rice University researchers find new possibilities for benign, ‘tunable’ virus
Rice University scientists have designed a tunable virus that works like a safe deposit box. It takes two keys to open it and release its therapeutic cargo.
The Rice lab of bioengineer Junghae Suh has developed an adeno-associated virus (AAV) that unlocks only in the presence of two selected proteases, enzymes that cut up other proteins for disposal. Because certain proteases are elevated at tumor sites, the viruses can be designed to target and destroy the cancer cells.
AAVs are fairly benign and have become the object of intense study as delivery vehicles for gene therapies. Researchers often try to target AAVs to cellular receptors that may be slightly overexpressed on diseased cells.
The Rice lab takes a different approach. “We were looking for other types of biomarkers beyond cellular receptors present at disease sites,” Suh said. “In breast cancer, for example, it’s known the tumor cells oversecrete extracellular proteases, but perhaps more important are the infiltrating immune cells that migrate into the tumor microenvironment and start dumping out a whole bunch of proteases as well.
“So that’s what we’re going after to do targeted delivery. Our basic idea is to create viruses that, in the locked configuration, can’t do anything. They’re inert,” she said. When programmed AAVs encounter the right protease keys at sites of disease, “these viruses unlock, bind to the cells and deliver payloads that will either kill the cells for cancer therapy or deliver genes that can fix them for other disease applications.”
Suh’s lab genetically inserts peptides into the self-assembling AAVs to lock the capsids, the hard shells that protect genes contained within. The target proteases recognize the peptides “and chew off the locks,” effectively unlocking the virus and allowing it to bind to the diseased cells.
“If we were just looking for one protease, it might be at the cancer site, but it could also be somewhere else in your body where you have inflammation. This could lead to undesirable side effects,” she said. “By requiring two different proteases – let’s say protease A and protease B – to open the locked virus, we may achieve higher delivery specificity since the chance of having both proteases elevated at a site becomes smaller.”
In the future, molecular-imaging approaches will be used to detect both the identity and concentration of elevated proteases. “With that information, we would be able to pick a virus device from our panel of engineered variants that has the right properties to target that disease site. That’s where we want to go,” she said.
Suh said elevated proteases are found around many diseased tissues. She suggested these protease-activatable viruses may be useful for the treatment of not only cancers but also neurological diseases, such as stroke, Parkinson’s and Alzheimer’s diseases, and heart diseases, including myocardial infarction and congestive heart failure.
The ultimate vision of this technology is to design viruses that can carry out a combination of steps for targeting. “To increase the specificity of virus unlocking, you can imagine creating viruses that require many more keys to open,” she said. “For example, you may need both proteases A and B as well as a cellular receptor to unlock the virus. The work reported here is a good first step toward this goal.”
The Latest on: Cancer therapy
via Google News
The Latest on: Cancer therapy
- Years later, cancer cases linger over 9/11 anniversaryon September 8, 2019 at 8:39 pm
Ten thousand of them have been diagnosed with cancer by the World Trade Center Health Program, a federal treatment program helping survivors. At the end of June this year, 21,000 people not considered ...
- IASLC World Conference on Lung Cancer--Press Briefing Summary from Sunday, September 8thon September 8, 2019 at 7:10 pm
"These data continue to show encouraging anti-tumor activity with AMG 510, underscoring the potential to close the treatment gap for non-small cell lung cancer patients with previously treated ...
- Tiny fish in SA lab may hold cure for rare canceron September 8, 2019 at 7:07 pm
Local 13-year-old Kennedie Bailey, who just beat that cancer, saw the little zebrafish that may lead to a new treatment for other kids and prevent tumors from returning. It was Mother's Day 2017 when ...
- Women With Breast Cancer Protest at Komen NYC Runon September 8, 2019 at 12:43 pm
The research funding proportion is far lower than some other high-profile breast cancer nonprofits, which invest as much as 80% to 90%. However, Komen's mission is multipronged and involves "advancing ...
- Breast Cancer Index® publishes new pivotal data strengthening clinical evidence as a predictive factor of benefit from endocrine therapyon September 8, 2019 at 12:12 pm
SAN DIEGO, Calif., September 5, 2019 – Biotheranostics, Inc. today announced new pivotal data on the Breast Cancer Index ® (BCI) published in the Annals of Oncology on August 28 th 2019 further ...
- Nivolumab combined with ipilimumab safe as first-line therapy for lung cancer patientson September 8, 2019 at 9:24 am
Combining the PD-1 immune check point inhibitor nivolumab with the monoclonal antibody ipilimumab showed a consistent safety profile in special populations with advanced non-small cell lung cancer ...
- Age affects efficacy of immunotherapy treatment for breast cancer, preclinical study revealson September 8, 2019 at 1:27 am
Recent clinical trials have indicated that immune checkpoint blockade (ICB) therapy, which is designed to unleash a patient's immune system to attack cancer, has been revolutionary in its implications ...
- Cannabis During Breast Cancer Treatment: What Are The Benefits?on September 6, 2019 at 5:10 pm
A cancer diagnosis is a life-changing event. From the confusion of understanding the road ahead to the hectic schedule of treatment protocols and never-ending appointments, many individuals ...
- When Treatment Is Over: Actor Sterling Brown Puts a Spotlight on Life After Canceron September 6, 2019 at 10:26 am
Sign on to social media on any given day and you’re likely to encounter a certain genre of video posts — the last-day-of-treatment post. In it, someone who’s been undergoing treatment for cancer can ...
- Cancer Gene Therapy Market Growth Opportunities, Trends by Manufacturers, Regions, Application and Forecast to 2024on September 6, 2019 at 8:24 am
Sep 06, 2019 (AmericaNewsHour) -- The Cancer Gene Therapy Market report offers detailed competitive landscape of the global market. It includes company market share analysis, product portfolio of the ...
via Bing News