Basem Al-Shayeb

Last updated

Basem Al-Shayeb is an Egyptian American microbiologist who is a co-founder and the founding chief technology officer of Amber Bio, a biotechnology startup company in the San Francisco Bay Area which is developing multi-kilobase RNA editing therapies using CRISPR-Cas systems. [1] [2] [3] [4]

Al-Shayeb received his PhD in microbiology [5] [6] as a National Science Foundation Fellow at the University of California, Berkeley and Innovative Genomics Institute, [7] where he conducted his dissertation work in the lab of Jennifer Doudna, co-advised by Jillian Banfield in the Earth and Planetary Science Department. [8] According to ORCID records, he is an active peer reviewer for Nature Portfolio research for several journals including Nature, Nature Communications , and Multidisciplinary Journal of Microbial Ecology (ISME). [9]

Research

During his time at UC Berkeley, Al-Shayeb was first or co-first author on publications describing the discovery of the largest known bacteriophages reported in Nature , [10] [11] [12] the smallest CRISPR-Cas genome editing systems reported in Science Magazine and Cell [13] [14] [15] and a new form of extrachromosomal DNA elements, which Al-Shayeb and colleagues named "Borgs," [16] [17] found in methane-oxidizing archaea ( Methanoperedens spp.) reported in Nature . [18] Some of the aforementioned CRISPR-Cas enzymes were further licensed by Mammoth Biosciences for diagnostic and therapeutic development [19] and in partnership with Vertex, [20] Bayer, [21] and Regeneron [22] to boost precision of gene-editing "as well as easing delivery for use in actual living cells and combining different target edits in a so-called “multiplex” arrangement", as further referenced in the 2020 Nobel Prize Lecture. [23] Subsequently, he supervised research reporting a strategy for programmable editing of large RNA molecules. [24] He was listed in Forbes 30 Under 30 and Arab America's 30 Under 30 in 2021, [11] [25] and Forbes All-Star Alumni in 2024 for his scientific contributions. [26]

Related Research Articles

Gene knockdown is an experimental technique by which the expression of one or more of an organism's genes is reduced. The reduction can occur either through genetic modification or by treatment with a reagent such as a short DNA or RNA oligonucleotide that has a sequence complementary to either gene or an mRNA transcript.

<span class="mw-page-title-main">Insertion (genetics)</span> Type of mutation

In genetics, an insertion is the addition of one or more nucleotide base pairs into a DNA sequence. This can often happen in microsatellite regions due to the DNA polymerase slipping. Insertions can be anywhere in size from one base pair incorrectly inserted into a DNA sequence to a section of one chromosome inserted into another. The mechanism of the smallest single base insertion mutations is believed to be through base-pair separation between the template and primer strands followed by non-neighbor base stacking, which can occur locally within the DNA polymerase active site. On a chromosome level, an insertion refers to the insertion of a larger sequence into a chromosome. This can happen due to unequal crossover during meiosis.

<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.

Guide RNA (gRNA) or single guide RNA (sgRNA) is a short sequence of RNA that functions as a guide for the Cas9-endonuclease or other Cas-proteins that cut the double-stranded DNA and thereby can be used for gene editing. In bacteria and archaea, gRNAs are a part of the CRISPR-Cas system that serves as an adaptive immune defense that protects the organism from viruses. Here the short gRNAs serve as detectors of foreign DNA and direct the Cas-enzymes that degrades the foreign nucleic acid.

<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 pioneered work in CRISPR gene editing, and made other fundamental contributions in biochemistry and genetics. 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">Feng Zhang</span> Chinese–American biochemist

Feng Zhang is a Chinese–American biochemist. Zhang currently holds the James and Patricia Poitras Professorship in Neuroscience at the McGovern Institute for Brain Research and in the departments of Brain and Cognitive Sciences and Biological Engineering at the Massachusetts Institute of Technology. He also has appointments with the Broad Institute of MIT and Harvard. He is most well known for his central role in the development of optogenetics and CRISPR technologies.

<span class="mw-page-title-main">CRISPR interference</span> Genetic perturbation technique

CRISPR interference (CRISPRi) is a genetic perturbation technique that allows for sequence-specific repression of gene expression in prokaryotic and eukaryotic cells. It was first developed by Stanley Qi and colleagues in the laboratories of Wendell Lim, Adam Arkin, Jonathan Weissman, and Jennifer Doudna. Sequence-specific activation of gene expression refers to CRISPR activation (CRISPRa).

A protospacer adjacent motif (PAM) is a 2–6-base pair DNA sequence immediately following the DNA sequence targeted by the Cas9 nuclease in the CRISPR bacterial adaptive immune system. The PAM is a component of the invading virus or plasmid, but is not found in the bacterial host genome and hence is not a component of the bacterial CRISPR locus. Cas9 will not successfully bind to or cleave the target DNA sequence if it is not followed by the PAM sequence. PAM is an essential targeting component which distinguishes bacterial self from non-self DNA, thereby preventing the CRISPR locus from being targeted and destroyed by the CRISPR-associated nuclease.

<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.

<span class="mw-page-title-main">Cas12a</span> DNA-editing technology

Cas12a is a subtype of Cas12 proteins and an RNA-guided endonuclease that forms part of the CRISPR system in some bacteria and archaea. In CRISPR systems, Cas12a serves to destroy the genetic material of viruses and other foreign DNA, thereby protecting the cell from infection. Like other Cas enzymes, Cas12a binds to an RNA to target nucleic acid in a specific and programmable matter. In the host organism, the crRNA contains a constant region that is recognized by the Cas12a protein and a spacer region that is complementary to a piece of foreign nucleic acid that previously infected the cell.

<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.

Off-target genome editing refers to nonspecific and unintended genetic modifications that can arise through the use of engineered nuclease technologies such as: clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9, transcription activator-like effector nucleases (TALEN), meganucleases, and zinc finger nucleases (ZFN). These tools use different mechanisms to bind a predetermined sequence of DNA (“target”), which they cleave, creating a double-stranded chromosomal break (DSB) that summons the cell's DNA repair mechanisms and leads to site-specific modifications. If these complexes do not bind at the target, often a result of homologous sequences and/or mismatch tolerance, they will cleave off-target DSB and cause non-specific genetic modifications. Specifically, off-target effects consist of unintended point mutations, deletions, insertions inversions, and translocations.

<span class="mw-page-title-main">Rachel Haurwitz</span> American biochemist

Rachel Elizabeth Haurwitz is an American biochemist and structural biologist. She is the co-founder, chief executive officer, and president of Caribou Biosciences, a genome editing company.

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

CRISPR gene editing 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">Luciano Marraffini</span> American Microbiologist

Luciano Marraffini is an Argentinian-American microbiologist. He is currently professor and head of the laboratory of bacteriology at The Rockefeller University. He is recognized for his work on CRISPR-Cas systems, being one of the first scientists to elucidate how these systems work at the molecular level.

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

LEAPER is a genetic engineering technique in molecular biology by which RNA can be edited. The technique relies on engineered strands of RNA to recruit native ADAR enzymes to swap out different compounds in RNA. Developed by researchers at Peking University in 2019, the technique, some have claimed, is more efficient than the CRISPR gene editing technique. Initial studies have claimed that editing efficiencies of up to 80%.

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.

<span class="mw-page-title-main">Borg (microbiology)</span> Aspect of DNA sequences

A borg is a "giant extrachromosomal element with the potential to augment methane oxidation", described by Basem Al-Shayeb and Jill Banfield. Borgs are long DNA sequences existing alongside the main chromosome in the archaea Methanoperedens, in oxygen-starved environments such as deep mud. Borgs were discovered by Professor Jill Banfield and her team in the soil of a wetland, an aquifer, a riverbed, and a deserted mercury mine in the states of California and Colorado.

The Innovative Genomics Institute (IGI) is an American nonprofit scientific research institute founded by Nobel laureate and CRISPR gene editing pioneer Jennifer Doudna and biophysicist Jonathan Weissman. 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.

References

  1. ↑ Rice, India. "This Startup Just Raised $26 Million To Develop Safer Gene Editing Tools". Forbes. Retrieved 2024-06-27.
  2. ↑ "New RNA-Editing Company, Amber Bio, Launches Multi-Kilobase Editing Platform". GEN - Genetic Engineering and Biotechnology News. 2023-08-03. Retrieved 2024-06-27.
  3. ↑ https://www.businesswire.com/news/home/20230803489484/en/Amber-Bio-Raises-26-Million-Seed-Financing-Co-Led-by-Playground-Global-and-Andreessen-Horowitz-to-Advance-New-RNA-Based-Gene-Editing-Platform
  4. ↑ "RNA editing start-up Amber Bio launches with $26 million". Chemical & Engineering News. Retrieved 2024-06-27.
  5. ↑ "ORCID". orcid.org. Retrieved 2024-08-17.
  6. ↑ "Basem Al-Shayeb". Plant & Microbial Biology | University of California, Berkeley. Retrieved 2024-08-18.
  7. ↑ "Meet an IGI Scientist: Basem Al-Shayeb". Innovative Genomics Institute (IGI). Retrieved 2022-03-13.
  8. ↑ "Basem Al-Shayeb | Earth & Planetary Science". eps.berkeley.edu. Retrieved 2024-08-18.
  9. ↑ "ORCID". orcid.org. Retrieved 2024-09-15.
  10. ↑ Knapp, Alex. "30 Under 30 In Science 2021: Building Better Trees, Supernova Simulations And Holograms". Forbes. Retrieved 2024-09-15.
  11. 1 2 "Basem Al-Shayeb". Forbes. Retrieved 2022-03-13.
  12. ↑ York, Ashley (April 2020). "Too big to be ignored". Nature Reviews Microbiology. 18 (4): 192. doi:10.1038/s41579-020-0341-z. ISSN   1740-1534. PMID   32066943.
  13. ↑ "News: Tiny but Mighty: How Researchers Found a New Game-Changing CRISPR Tool". CRISPR Medicine. Retrieved 2024-08-15.
  14. ↑ "New Compact Genome Editors Found in Viruses". Innovative Genomics Institute (IGI). Retrieved 2024-08-17.
  15. ↑ Al-Shayeb, Basem; Skopintsev, Petr; Soczek, Katarzyna M.; Stahl, Elizabeth C.; Li, Zheng; Groover, Evan; Smock, Dylan; Eggers, Amy R.; Pausch, Patrick; Cress, Brady F.; Huang, Carolyn J.; Staskawicz, Brian; Savage, David F.; Jacobsen, Steven E.; Banfield, Jillian F. (2022-11-23). "Diverse virus-encoded CRISPR-Cas systems include streamlined genome editors". Cell. 185 (24): 4574–4586.e16. doi: 10.1016/j.cell.2022.10.020 . ISSN   0092-8674. PMID   36423580.
  16. ↑ "Scientists discover Borgs, DNA strands that assimilate genes from their hosts". Chemical & Engineering News. Retrieved 2024-08-17.
  17. ↑ Rinke, Christian (October 2022). "Mystery find of microbial DNA elements called Borgs". Nature. 610 (7933): 635–637. Bibcode:2022Natur.610..635R. doi:10.1038/d41586-022-02975-3. PMID   36261713.
  18. ↑ "Previously undiscovered DNA 'borgs' found on California wetlands". The Independent. 2021-07-30.
  19. ↑ Etherington, Darrell (2020-08-12). "Mammoth Biosciences lands exclusive license to new CRISPR proteins that could boost gene editing precision". TechCrunch. Retrieved 2024-09-15.
  20. ↑ "Jennifer Doudna's Mammoth Links with Vertex in $700 Million Ultra-Small CRISPR Deal". BioSpace. 2021-10-26. Retrieved 2024-09-15.
  21. ↑ Liu, Angus. "JPM 2022: Bayer taps CRISPR science from Doudna's lab in $1B biobucks Mammoth gene therapy deal".
  22. ↑ "Small Enzymes, Giant Leaps: CRISPR's Next-Generation Approach to Genetic Diseases". BioSpace. 2024-08-05. Retrieved 2024-09-15.
  23. ↑ Grandin, Karl (2024-02-21). The Nobel Prizes 2020. World Scientific. ISBN   978-981-12-9012-1.
  24. ↑ Borrajo, Jacob; Javanmardi, Kamyab; Griffin, James; St. Martin, Susan J.; Yao, David; Hill, Kaisle; Blainey, Paul C.; Al-Shayeb, Basem (2023-08-18). "Programmable multi-kilobase RNA editing using CRISPR-mediated trans-splicing". bioRxiv: 2023.08.18.553620. doi:10.1101/2023.08.18.553620. PMC   10462116 . PMID   37645763.
  25. ↑ "Arab America Foundation Announces 30 Under 30 Awardees-Class of 2021". Arab America. 2021-10-06. Retrieved 2022-10-04.
  26. ↑ "Forbes 30 Under 30 2024: Science". Forbes. Retrieved 2024-08-17.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.