Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Rice Writes Rules for Gene-Therapy Vectors

Published: Thursday, August 15, 2013
Last Updated: Thursday, August 15, 2013
Bookmark and Share
Researchers compute, then combine benign viruses to fight disease.

Rice University researchers are making strides toward a set of rules to custom-design Lego-like viral capsid proteins for gene therapy.

A new paper by Rice scientists Junghae Suh and Jonathan Silberg and their students details their use of computational and bioengineering methods to combine pieces of very different adeno-associated viruses (AAVs) to create new, benign viruses that can deliver DNA payloads to specific cells.

The research appears this month in the American Chemical Society journal ACS Synthetic Biology.
AAVs are found in nature and commonly infect humans but cause no disease. That makes them good candidates to serve as carriers that target cells and deliver genes to treat diseases.

The team, which included graduate student and lead author Michelle Ho and undergraduates Benjamin Adler and Michael Torre, wants to define rules to design a variety of viruses that deliver therapeutic genes. They used computer models to find likely AAV candidates for recombination and then tested the model predictions by engineering 17 unique virus capsid proteins and evaluating their ability to fold and assemble into capsid-encased viruses.

Gene therapy shows promise in the treatment of not only genetic disorders but also cancer and cardiovascular diseases, said Suh, an assistant professor of bioengineering at Rice’s BioScience Research Collaborative.

“But you need a mechanism to get the correct gene into the human body and to the target cells,” she said. “To do that, people use gene vectors, and viruses encompass the largest category of vectors. They’ve naturally evolved to deliver genes into the body. Our goal is to reprogram them to target specific organs or tissues.

“The big challenge is to go about this in a rational manner,” she said. “People have done a lot of work to solve the structure of viruses. We know what they look like. The question is: How can we use that information to guide the design of our viral vectors?”

The team’s answer starts with the “SCHEMA” algorithm they adapted to predict how parts of very large viruses can recombine by homing in on the viral protein sequences that work well together.
Silberg, an associate professor of biochemistry and cell biology, said approaches to virus design can lean either toward brute force – “Let’s make 1,000 of them and maybe we’ll get lucky” – or purely computational, where a biophysicist will try to predict the role of small changes to the virus capsid.

“We’re working on a hybrid approach,” he said. “Instead of making a random library (of viruses) or computationally designing a single virus, which has a low frequency of working, we’re trying to make smart libraries. We’re learning to adapt computer programs used for small proteins with a few thousand atoms for viruses with more than 100,000 atoms.”

Rather than target mutations in particular viruses, the researchers used the program to compare parts from different but related viruses to see if they would combine together to form new viruses.
“We’re treating them like Legos,” Silberg said. “We’re taking distantly related viruses that nature might not recombine very efficiently and looking for self-contained pieces of these proteins that can be swapped.”

The “parent” viruses were AAV serotype 2, which Suh said is the most commonly studied for gene therapy today, and AAV serotype 4. “They’re part of the same virus family, but genetically, AAV4 is one of the most different from AAV2.”

She said it has been difficult for researchers in the past to rationally make chimeras – one organism that combines parts of two or more genetically distinct elements – from these viruses using traditional techniques.

But Suh’s lab confirmed the chimeric structures predicted by the computer models could be made into real hybrid viruses. Now the challenge is to make a much larger library of chimeric viruses to establish a statistically solid set of guidelines.

“We want to know how to make a more stable virus, or a virus that switches its conformation after it enters a cell,” Silberg said.

“And we want to know how to make one that goes not only just to the brain, but to a specific part of the brain to target a neurodegenerative disease,” Suh added. “The bottom line is that we want these rules.”

Silberg said the researchers had expected to confirm that the SCHEMA algorithm could efficiently predict recombinations that could deliver cargo to cells. “But we also learned something really surprising: that you can beat these viruses up a lot more than you can small proteins, and they still assemble into large virus particles,” he said. “It’s really interesting that viruses fundamentally seem to tolerate the kind of mutation we’re doing.”

The Keck Center of the Gulf Coast Consortia Nanobiology Interdisciplinary Graduate Training Program (through a grant from the National Institute of Biomedical Imaging and Bioengineering), the Robert A. Welch Foundation and the National Science Foundation supported the research.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Chemical Design Made Easier
Rice University scientists prepare elusive organocatalysts for drug and fine chemical synthesis.
Wednesday, November 25, 2015
Biomarker Finder Adjusts On the Fly
Rice University scientists build better tool to find signs of disease.
Thursday, October 22, 2015
Gene On-Off Switch Works Like Backpack Strap
Texas Medical Center-based team unravels how loops form in genome.
Thursday, October 22, 2015
Structure of Protein at Root of Muscular Disease Decoded
Researchers at Rice University and Baylor College of Medicine have unlocked the structural details of a protein seen as key to treating a neuromuscular disease.
Thursday, October 01, 2015
Researchers Find New Clue to Halting Leukemia Relapse
A protein domain once considered of little importance may be key to helping patients who are fighting acute myeloid leukemia (AML) avoid a relapse.
Friday, September 11, 2015
Imaging Software Could Speed Breast Cancer Diagnosis
Technology could improve access to diagnostic services in developing countries.
Wednesday, August 26, 2015
Researchers Strategize to Outsmart Bacteria
Rice University lab identifies mutations that allow bacteria to resist antibiotics.
Thursday, August 06, 2015
Cancer Treatment Models get Real
Researchers at Rice Univ. and Univ. of Texas MD Anderson Cancer Center have developed a way to mimic the conditions under which cancer tumors grow in bones.
Thursday, August 06, 2015
Bacteria Use DNA Replication to Time Key Decision
Rice University researchers have found that in spore-forming bacteria, chromosomal locations of genes can couple the DNA replication cycle to critical decisions about whether to reproduce or form spores.
Monday, July 13, 2015
Massive Genome Shift in one Generation
A team of biologists has discovered that an agricultural pest that began plaguing U.S. apple growers in the 1850s likely did so after undergoing extensive and genome-wide changes in a single generation.
Tuesday, June 16, 2015
DNA Mutations get Harder to Hide
Rice University researchers have developed a method to detect rare DNA mutations with an approach hundreds of times more powerful than current methods.
Wednesday, May 27, 2015
Amniotic Stem Cells Demonstrate Healing Potential
Rice University, Texas Children’s Hospital study proves cells promote vasculature in hydrogel therapy.
Friday, April 10, 2015
Cells Exercise Suboptimal Strategy to Survive
Rice University study shows it’s not always good for cells’ metabolism to work at peak efficiency.
Thursday, April 09, 2015
Designing A Better Way To Study Stomach Flu
Texas Medical Center team aims to improve research of gastrointestinal disease.
Wednesday, March 18, 2015
Worm Virus Details Come to Light
Rice University scientists have won a race to find the crystal structure of rare nematode virus, known to infect the most abundant animal on Earth.
Wednesday, August 20, 2014
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
How a Genetic Locus Protects Adult Blood-Forming Stem Cells
Mammalian imprinted Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells' mitochondria.
Genetic Basis of Fatal Flu Side Effect Discovered
A group of people with fatal H1N1 flu died after their viral infections triggered a deadly hyperinflammatory disorder in susceptible individuals with gene mutations linked to the overactive immune response, according to a recent study.
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
The MaxSignal Colistin ELISA Test Kit from Bioo Scientific
Kit can help prevent the antibiotic apocalypse by keeping last resort drugs out of the food supply.
"Good" Mozzie Virus Might Hold Key to Fighting Human Disease
Australian scientists have discovered a new virus carried by one of the country’s most common pest mosquitoes.
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos