Center for Molecular Biology of RNA

The UCSC RNA Center welcomes faculty Carol Greider and Sarah Loerch,

The UCSC COVID Ribozyme Project

Coronaviruses, which cause SARS, MERS and COVID-19 are RNA viruses - that is, their genetic information is encoded in RNA instead of DNA. This fact has caught the attention of researchers in the Center for Molecular Biology of RNA at UCSC. The Center is the largest and most prominent grouping of RNA researchers in the world, with 20 RNA research groups, three members of the National Academy of Sciences, a Nobel laureate and a Breakthrough laureate. The two research groups of William Scott and Harry Noller are leading the COVID Ribozyme Project, whose goal is to design a 'ribozyme' (a catalytic RNA molecule) to attack the RNA genome of SARS-CoV-2, the coronavirus responsible for the world-wide COVID-19 pandemic. Professor Scott, who is a world leader in the field of ribozyme research, has developed a small, powerful ribozyme that can be designed to attack and cut virtually any viral RNA. In the case of coronaviruses, the cut will disable the virus's ability to replicate itself during infection. Initial experiments, in collaboration with Noller's group, have already identified four ribozyme designs that rapidly and specifically cut SARS-CoV-2 RNA targets in the test tube. Preliminary experiments now show that at least one of these ribozymes can attack its RNA target in human cells. Future experiments will be aimed toward asking whether these ribozymes can inactivate a live virus in infected cells and animal models. In addition to Profs. Noller and Scott, the collaboration has been critically dependent on the expertise of Dr. Sara O’Rourke, a UCSC virologist with extensive previous background working with human RNA viruses, and Dr. Laura Lancaster, an RNA Center molecular biologist whose focus is on ribosomes and protein synthesis. The ribozymes are designed to target the most vulnerable and invariant sequences of SARS-CoV-2, including the gene encoding the infamous 'spike protein', which forms the knobs seen on the surface of the virus seen in electron microscope images. The spike protein is especially critical, because it recognizes and binds to a receptor on the surfaces of cells in the human respiratory tract, contributing to the unusually high infectiousness of the virus. However, researchers believe that even a cut anywhere in the virus RNA will inactivate its infectious capabilities.

Although several research groups and companies around the world are attempting to fast-track the development of a vaccine against SARS-CoV-2, effective treatments are nevertheless urgently needed for the millions currently infected world-wide. Furthermore, fast-tracking vaccine development will require shortcuts in testing such as human-challenge trials. In this type of trial, healthy patients are treated with a candidate vaccine, and then challenged with exposure to live virus to see if they have developed immunity. However, human-challenge trials can only be safely conducted if there is a treatment in case the vaccine fails. Development of an effective anti-COVID ribozyme could provide precisely such a treatment, allowing accelerated development of an effective vaccine.

Ribozymes are an especially attractive potential therapy for other reasons. First, they only target RNAs, so even if a ribozyme inadvertantly attacks a human RNA, RNAs are constantly being replaced in cells, and so our systems will rapidly recover. Second, we are further protected from any potential side-effects by the fact that that the ribozyme itself, being RNA, will soon be degraded. Third, RNAs have been found to enter human cells relatively easily, and effective RNA delivery systems have been developed in recent years. Because the SARS-CoV-2 virus infects the respiratory tract, delivery of an anti-COVID ribozyme could be as simple as using a nasal spray.

Importantly, RNA viruses, such as influenza, are well known to develop resistance to vaccines because they undergo mutations over time in the human population. These are usually mutations that cause changes in proteins on the surface of the virus. But Professor Scott has designed his ribozymes to attack RNA sequences that are completely invariant in all coronaviruses. So even when the next deadly coronavirus emerges, its target sequences will almost surely be unchanged, so will be knocked out by the ribozyme.

Finally, it is worth noting that most human viruses, including HIV, polio, influenza, rabies and even the common cold, are RNA viruses. Accordingly, there is no obvious reason why Scott's ribozymes could not be designed to attack any human RNA virus. In fact, Scott's group and his associated startup company IncisiveRNA, founded at the local Startup Sandbox incubator in Santa Cruz, are already developing candidate HIV-specific ribozymes for treatment of AIDS.

June 22, 2017 - Exploring Biology's Dark Matter: RNA

April 1, 2017 - Assistant Professor Angela Brooks Named "Scientist To Watch" By The Scientist Magazine

December 4,2016 - Harry Noller wins the 2017 Life Sciences Breakthrough Prize!

October 5, 2016 - Local group funds four UC Santa Cruz cancer researchers

May 19, 2016 - Malignancy-associated gene network regulated by an RNA binding protein

April 21, 2016 - MCD Biology faculty land new research funding

April 18, 2016 - Carpenter Lab researches role of lncRNA in autoimmune disorders

March 14, 2016 - Leukemia study reveals role of RNA binding protein in driving cancer

October 5, 2015 - Study reveals key structure in telomerase enzyme, a target for cancer drugs

Summer, 2015 - International RNA Summit, UCSC, Aug 10-14, 2015

August 6, 2014 - NIH Awards $2 Million To UCSC Group For DNA Sequencing Research

Summer, 2014 - Gathering of The Ribe Tribe!

May 29, 2014 - UCSC receives major grant to revamp introductory science courses

March, 2014 - The International RNA Summit!

October 31, 2013 - Biologist Manuel Ares receives Outstanding Faculty Award

July, 2013 - Ribosomes Conference 2013, Napa California

January 17, 2013 - Novel technique reveals dynamics of telomere DNA structure

September, 2011 - Congratulations to Dr. Harry Noller for winning The Aminoff Prize 2012!

September, 2011 - Neanderthal genome yields insights into human evolution and evidence of interbreeding

After extracting ancient DNA from the 40,000-year-old bones of Neanderthals, scientists have obtained a draft sequence of the Neanderthal genome.

April, 2010 - Four UCSC professors elected to American Academy of Arts and Sciences

January, 2010 - UCSC researchers trace the roots of a type of muscular dystrophy

November 22, 2009 - Building the Genome Zoo. Robert Pollie Podcast interview with David Haussler

Winter, 2008 - Dr Michael Stone continues the trend and joins the Center for Molecular Biology of RNA

Fall, 2008 - Dr. Jeremy Sanford joins the Center for Molecular Biology of RNA

Fall, 2008 - Researchers find new mode of gene regulation in mammals

Researchers at the University of California, Santa Cruz, have discovered a type of gene regulation never before observed in mammals--a "ribozyme" that controls the activity of an important family of genes in several different species.

June 6, 2008 - Science Daily: Molecular 'Ratcheting' Of Single Ribosome Molecules Observed In Act Of Building Proteins

Researchers have reported that they are the first to observe the dynamic, ratchet-like movements of single ribosomal molecules in the act of building proteins from genetic blueprints.

March 15, 2007 - RNA enzyme structure offers a glimpse into the origins of life

Researchers at the University of California, Santa Cruz, have determined the three-dimensional structure of an RNA enzyme, or "ribozyme," that carries out a fundamental reaction required to make new RNA molecules. Their results provide insight into what may have been the first self-replicating molecule to arise billions of years ago on the evolutionary path toward the emergence of life.

September 13, 2006 - Researchers probe the machinery of cellular protein factories

Proteins of all sizes and shapes do most of the work in living cells, and the DNA sequences in genes spell out the instructions for making those proteins. The crucial job of reading the genetic instructions and synthesizing the specified proteins is carried out by ribosomes, tiny protein factories humming away inside the cells of all living things.

March 15, 2007 - Newly discovered gene may hold clues to evolution of human brain capacity

Scientists have discovered a gene that has undergone accelerated evolutionary change in humans and is active during a critical stage in brain development. Although researchers have yet to determine the precise function of the gene, the evidence suggests that it may play a role in the development of the cerebral cortex and may even help explain the dramatic expansion of this part of the brain during human evolution.

July 20, 2006 - Atomic-resolution structure of a ribozyme yields insights into RNA catalysis and the origins of life

Which came first, nucleic acids or proteins? This question is molecular biology's version of the "chicken-or-the-egg" riddle. Genes made of nucleic acids (DNA or RNA) contain the instructions for making proteins, but enzymes made of proteins are needed to replicate genes. For those who try to understand how life originated, this once seemed an intractable paradox.

April 23, 2006 - Santa Cruz Sentinel: Stem cell research under way at UCSC

The cause of diabetes, cancer, Alzheimer's and Parkinson's continues to puzzle the world. But while cures may be a long way off, research into genetics and biomedicine--some of it happening right here--provides hope, and stem cell scientists at UC Santa Cruz are being touted as the "next generation" of researchers.

April 3, 2006 - UCSC researchers receive $1.6 million grant for biosensor project

A team of UCSC researchers has received major funding from the National Institutes of Health to develop new sensor technology for biomedical applications.