Innovative Genomics Institute

Last updated
Innovative Genomics Institute
Founder(s) Jennifer Doudna and Jonathan Weissman
Established2015;9 years ago (2015)
Focus Gene editing, CRISPR, genomics, human health, sustainable agriculture, climate change
President Jennifer Doudna
Key people Jennifer Doudna, Bradley Ringeisen, Jillian Banfield, Fyodor Urnov, Alex Marson, Brian Staskawicz, Pamela Ronald
Address2151 Berkeley Way, Berkeley, CA, 94720
Location
University of California, Berkeley
,
Berkeley
,
California
,
USA
Coordinates 37°52′27″N122°16′00″W / 37.874044757682164°N 122.26678015439391°W / 37.874044757682164; -122.26678015439391
Website www.innovativegenomics.org

The Innovative Genomics Institute (IGI) is a nonprofit scientific research institute founded by Nobel laureate and CRISPR gene editing pioneer Jennifer Doudna and biophysicist Jonathan Weissman. [1] [2] The institute is based at the University of California, Berkeley, and also has member researchers at the University of California, San Francisco, UC Davis, UCLA, Lawrence Berkeley National Laboratory, Lawrence Livermore National Laboratory, Gladstone Institutes, and other collaborating research institutions. The IGI focuses on developing real-world applications of genome editing to address problems in human health, agriculture and climate change. [3] [4]

Contents

In addition to Doudna, current IGI directors and investigators include Jillian Banfield, who first introduced Doudna to CRISPR systems in bacteria in 2006, [5] [6] Fyodor Urnov, who coined the term "genome editing" with colleagues in 2005, [7] [8] as well as Alex Marson, Brian Staskawicz, and Pamela Ronald. [9] [10] The current executive director is Bradley Ringeisen, former director of the Biological Technologies Office at DARPA, who joined the IGI in 2020. [11] [12]

History

The first paper demonstrating the use of CRISPR-Cas9 as a programmable genome editing tool was published in 2012 by Doudna, Emmanuelle Charpentier and colleagues, [13] work that would result in Doudna and Charpentier being awarded the 2020 Nobel Prize in Chemistry. [14] Around this time, for-profit companies started forming to commercialize CRISPR in various ways, including Caribou Biosciences, Editas Medicine, and CRISPR Therapeutics. While Doudna was involved in some of commercial ventures, she also felt that a nonprofit institute could play a unique role in driving the science forward and helping develop ethical guidelines and equitable access to gene-editing technology in ways that market-driven companies would not, particularly because CRISPR held so much promise for addressing rare diseases that had often been neglected by the pharmaceutical industry. [3] [15] [16] [17] [18]

Jennifer Doudna at the Innovative Genomics Institute in 2021 Jennifer Doudna in 2021 at the Innovative Genomics Institute 02.jpg
Jennifer Doudna at the Innovative Genomics Institute in 2021

The formation of the IGI was initially announced in March 2014 as the "Innovative Genomics Initiative", a partnership between UC Berkeley and UCSF researchers and biopharmaceutical industry partners with the aim of enhancing and genome-editing technology and applying it to drug development and global health, with funding support from the Li Ka Shing Foundation and the two universities. [19] The official launch event was held on February 4, 2015. [20] [2] Early projects at the IGI focused on studying the use of CRISPR to address severe combined immunodeficiency disease and sickle cell disease. The IGI partnered with AstraZeneca and Agilent Technologies in 2015 to identify potential gene targets related to cancer, cardiovascular disease, autoimmune and inflammatory diseases, and other diseases with genetic components. [20] [2] [21]

In January 2017, the IGI relaunched as the Innovative Genomics Institute and moved into their current building on the UC Berkeley campus. At the same time, new sources of funding allowed the institute expanded its scope to apply CRISPR and other genomic technologies to plants and agriculture, and the IGI brought in Brian Staskawicz as the director of this program. [22] In early 2020, IGI co-founder Jonathan Weissman left UCSF and the IGI to take on the role of Landon T. Clay Professor of Biology at Whitehead Institute and professor of Biology at Massachusetts Institute of Technology. [23]

On March 9, 2020, UC Berkeley announced the suspension in-person classes and began shutting down many campus buildings due to the COVID-19 pandemic. [24] [25] On March 13, 2020, Doudna convened a meeting with IGI leadership to discuss whether the institute should temporarily shut down. Instead, they decided to rapidly launch a diagnostic testing facility in the IGI building to provide testing to the UC Berkeley community as well as first responders and underserved populations in the surrounding cities. [26] [27] [16] In addition to providing testing, the IGI awarded funding to support research studies into COVID-19 biology, epidemiology, public health impact, as well as novel diagnostics and therapeutic approaches. [28] [29] The IGI testing lab processed over 600,000 patient samples. [1] Doudna has said that the IGI's experience with the COVID-19 response and rapid large-team science changed the way the institute selected projects moving forward because it showed how much impact can be made when researchers work together on a common goal. [30] [1]

On October 7, 2020, the Nobel Prize in Chemistry was awarded to Doudna and Charpentier for their work on developing CRISPR-Cas9 gene editing. [31] [32] Doudna was unable to attend the traditional live awards ceremony in Stockholm due to the COVID-19 pandemic, so she accepted the award at her home in Berkeley, California, and celebrations were held at the IGI building. [14] [33] [34]

In October 2023, UC Berkeley announced plans to build a new "innovation zone" in downtown Berkeley with laboratory buildings that would provide new space for the IGI. [35]

Research Areas

IGI research centers around genome editing, incorporating researchers focused on human health applications, agricultural applications, development of genome-editing technology, and translation of lab discoveries into real-world solutions.

Advancing Genome Engineering

Since its founding, IGI researchers have discovered multiple new genome-editing proteins, expanding the toolkit beyond Cas9. [36] The wave of discoveries of additional genome-editing tools with different properties, including new Cas proteins and techniques like base editing, was sometimes called "CRISPR 2.0" in popular science reporting. [37] [38] Ultra-compact proteins CasX and CasY were discovered by Jillian Banfield and collaborators at the IGI in some of the world's smallest microbes. [39] [40] Another compact Cas protein, CasΦ ("Cas phi"), was discovered by Banfield and Doudna and colleagues in the genomes of huge bacteriophages. [41] [42] Doudna and other IGI researchers have also advanced new techniques to improve non-viral and in vivo delivery of CRISPR-based therapeutics for medical applications, and worked on improving CRISPR safety and precision. [43] [44] [45] [46]

Human Health

The IGI human health program has focused on developing therapies for rare and neglected genetic diseases and platform technology approaches to addressing rare diseases, including sickle cell disease and other blood and immune disorders. [47] In 2021, the US Food and Drug Administration approved a clinical trial for an experimental CRISPR-based therapy for sickle cell disease developed by a consortium including the IGI, UCSF Benioff Children's Hospital, and the UCLA Broad Stem Cell Research Center. [48] Other health research at the IGI focuses on cancer, [49] [50] neurodegenerative diseases, [51] [52] and clinical diagnostics. [53] [54]

Climate & Sustainable Agriculture

The IGI sustainable agriculture program and its Plant Genomics and Transformation Facility has developed CRISPR protocols for editing over 30 common crop species, [17] and has worked on developing applications including protecting the world's chocolate supply from cacao swollen shoot virus, [55] [56] removing toxic cyanide precursors in cassava, [57] and improving drought tolerance in rice. [58]

In 2022, the IGI launched new programs to apply genome editing and genomic technologies to the challenge of mitigating and adapting to climate change. [59] This work included efforts to reduce agricultural emissions, capture atmospheric carbon, and help farmers adapt to changing conditions. The Chan Zuckerberg Initiative committed $11 million to the IGI to support research on CRISPR-based approaches to enhancing the ability of plants and soils to remove and sequester atmospheric carbon. [10] [60]

At the 2023 TED conference in Vancouver, it was announced that the IGI was selected for funding by the Audacious Project and the institute received $70 million from donors to develop microbiome editing tools that can be applied to real-world problems related to human health and climate change. The project, entitled "Engineering the Microbiome with CRISPR to Improve our Climate and Health," is initially targeting two problems caused by microbiomes, methane emissions from livestock, and childhood asthma. [61] [62] [1]

Public Impact

An IGI team focuses on public impact works across disciplines to shape the impact of genome-editing research on society through research in ethics, law, economics, and policy. [63]

In a meeting with US senators in December 2018, Doudna was asked about the potential high cost of a CRISPR-based treatment of sickle cell disease and what could be done to bring these costs down. When she returned to the IGI following this meeting, she decided to make affordability a part of the mission of the IGI, and a key goal for its sickle cell initiative. [16]

In 2022, the IGI convened a group of 30 experts from diverse fields, including biotech, economics, manufacturing, venture capital, and intellectual property, to develop a plan to improve the affordability of genetic medicines. Current gene therapies and genome editing therapies can cost in the range of $2 to $3 million per patient. The group developed a report entitled "Making Genetic Therapies Affordable and Accessible" that developed strategies for reducing the cost of genetic medicines by a factor of 10 through a combination of new funding models, improved manufacturing, and alternative IP licensing approaches. [64] [65] [66] [67]

CRISPR Education

In addition to CRISPR research, the IGI works to advance public understanding of CRISPR and genome engineering and guide the ethical use of these technologies. Free public resources include:

Related Research Articles

<span class="mw-page-title-main">Gene therapy</span> Medical field

Gene therapy is a medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells.

<span class="mw-page-title-main">Human genetic enhancement</span> Technologies to genetically improve human bodies

Human genetic enhancement or human genetic engineering refers to human enhancement by means of a genetic modification. This could be done in order to cure diseases, prevent the possibility of getting a particular disease, to improve athlete performance in sporting events, or to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. These genetic enhancements may or may not be done in such a way that the change is heritable.

<span class="mw-page-title-main">Designer baby</span> Genetically modified human embryo

A designer baby is a baby whose genetic makeup has been selected or altered, often to exclude a particular gene or to remove genes associated with disease. This process usually involves analysing a wide range of human embryos to identify genes associated with particular diseases and characteristics, and selecting embryos that have the desired genetic makeup; a process known as preimplantation genetic diagnosis. Screening for single genes is commonly practiced, and polygenic screening is offered by a few companies. Other methods by which a baby's genetic information can be altered involve directly editing the genome before birth, which is not routinely performed and only one instance of this is known to have occurred as of 2019, where Chinese twins Lulu and Nana were edited as embryos, causing widespread criticism.

<span class="mw-page-title-main">CRISPR</span> Family of DNA sequence found in prokaryotic organisms

CRISPR is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacteriophages that had previously infected the prokaryote. They are used to detect and destroy DNA from similar bacteriophages during subsequent infections. Hence these sequences play a key role in the antiviral defense system of prokaryotes and provide a form of acquired immunity. CRISPR is found in approximately 50% of sequenced bacterial genomes and nearly 90% of sequenced archaea.

<span class="mw-page-title-main">Gene targeting</span> Genetic technique that uses homologous recombination to change an endogenous gene

Gene targeting is a biotechnological tool used to change the DNA sequence of an organism. It is based on the natural DNA-repair mechanism of Homology Directed Repair (HDR), including Homologous Recombination. Gene targeting can be used to make a range of sizes of DNA edits, from larger DNA edits such as inserting entire new genes into an organism, through to much smaller changes to the existing DNA such as a single base-pair change. Gene targeting relies on the presence of a repair template to introduce the user-defined edits to the DNA. The user will design the repair template to contain the desired edit, flanked by DNA sequence corresponding (homologous) to the region of DNA that the user wants to edit; hence the edit is targeted to a particular genomic region. In this way Gene Targeting is distinct from natural homology-directed repair, during which the ‘natural’ DNA repair template of the sister chromatid is used to repair broken DNA. The alteration of DNA sequence in an organism can be useful in both a research context – for example to understand the biological role of a gene – and in biotechnology, for example to alter the traits of an organism.

<span class="mw-page-title-main">Genome editing</span> Type of genetic engineering

Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly inserts genetic material into a host genome, genome editing targets the insertions to site-specific locations. The basic mechanism involved in genetic manipulations through programmable nucleases is the recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases, and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ).

<span class="mw-page-title-main">Jennifer Doudna</span> American biochemist and Nobel laureate (born 1964)

Jennifer Anne Doudna is an American biochemist who has done pioneering work in CRISPR gene editing, and made other fundamental contributions in biochemistry and genetics. Doudna was one of the first women to share a Nobel in the sciences. She received the 2020 Nobel Prize in Chemistry, with Emmanuelle Charpentier, "for the development of a method for genome editing." She is the Li Ka Shing Chancellor's Chair Professor in the department of chemistry and the department of molecular and cell biology at the University of California, Berkeley. She has been an investigator with the Howard Hughes Medical Institute since 1997.

<span class="mw-page-title-main">Cas9</span> Microbial protein found in Streptococcus pyogenes M1 GAS

Cas9 is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic engineering applications. Its main function is to cut DNA and thereby alter a cell's genome. The CRISPR-Cas9 genome editing technique was a significant contributor to the Nobel Prize in Chemistry in 2020 being awarded to Emmanuelle Charpentier and Jennifer Doudna.

<span class="mw-page-title-main">Emmanuelle Charpentier</span> French microbiologist, biochemist and Nobel laureate

Emmanuelle Marie Charpentier is a French professor and researcher in microbiology, genetics, and biochemistry. As of 2015, she has been a director at the Max Planck Institute for Infection Biology in Berlin. In 2018, she founded an independent research institute, the Max Planck Unit for the Science of Pathogens. In 2020, Charpentier and American biochemist Jennifer Doudna of the University of California, Berkeley, were awarded the Nobel Prize in Chemistry "for the development of a method for genome editing". This was the first science Nobel Prize ever won by two women only.

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J. Keith Joung is an American pathologist and molecular biologist who holds the Robert B. Colvin Endowed Chair in Pathology at Massachusetts General Hospital and is Professor of Pathology at Harvard Medical School. He is a leading figure in the field of genome editing and has pioneered the development of designer nucleases and sensitive off-target detection methods.

<span class="mw-page-title-main">Intellia Therapeutics</span> American biotechnology company

Intellia Therapeutics, Inc. is an American clinical-stage biotechnology company focused on developing novel, potentially curative therapeutics leveraging CRISPR-based technologies. The company's in vivo programs use intravenously administered CRISPR as the therapy, in which the company's proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues. Intellia's ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases.

Alexander Marson is an American biologist and infectious disease doctor who specializes in genetics, human immunology, and genome engineering. He is the Director of the Gladstone-UCSF Institute of Genomic Immunology, and a tenured Professor with a dual appointment in the Department of Medicine and the Department of Microbiology & Immunology at the University of California, San Francisco (UCSF).

<span class="mw-page-title-main">Lei Stanley Qi</span> Chemical and systems biology researcher

Lei "Stanley" Qi is an associate professor in the department of bioengineering, and the department of chemical and systems biology at Stanford University. Qi led the development of the first catalytically dead Cas9 lacking endonuclease activity (dCas9), which is the basis for CRISPR interference (CRISPRi). His laboratory subsequently developed CRISPR-Genome Organization (CRISPR-GO).

<span class="mw-page-title-main">He Jiankui affair</span> 2018 scientific and bioethical controversy

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<span class="mw-page-title-main">CRISPR gene editing</span> Gene editing method

CRISPR gene editing standing for "Clustered Regularly Interspaced Short Palindromic Repeats" is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR-Cas9 antiviral defense system. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added in vivo.

<span class="mw-page-title-main">CRISPR Therapeutics</span> Swiss-American biotechnology company

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Mammoth Biosciences is a biotechnology company based in Brisbane, California developing diagnostic tests using CRISPR-Cas12a and CRISPR-based therapies using its proprietary ultra-small CRISPR systems. Several CRISPR-Cas systems identified through the company's metagenomics-based protein discovery platform, including members of the Casφ and Cas14 families of CRISPR-associated enzymes, have demonstrated potential for therapeutic genome editing in in vivo settings.

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