Cas proteins

Extracted Attributes

• Origin

  Prokaryotic organisms (bacteria and archaea) as an adaptive immune system against viruses and plasmids

• Function

  RNA-guided nucleases that recognize and cleave specific DNA sequences

• Mechanism

  Utilize CRISPR sequences as guides to recognize and open specific DNA strands

• Key Protein

  Cas9 (CRISPR-associated protein 9)

• Applications

  Basic biological research, development of biotechnological products, treatment of diseases, life sciences, agriculture technology, industrial biotechnology, genetic disease treatment

• Size of CasΦ

  ~70-80 kilodaltons, approximately half the size of Cas9 and Cas12

• Discovery of CasΦ

  Found in megaphages (largest known bacteria-infecting viruses)

• Type V Cas Proteins

  Cas12a (Cpf1), Cas12b (C2c1), Cas12c (C2c3), Cas12d (CasY), Cas12e (CasX)

• OpenCrisper-1 Efficacy

  More effective than existing CRISPR technology

• OpenCrisper-1 Strategy

  Open-source to bypass restrictive patent landscapes

• OpenCrisper-1 Technology

  AI-driven gene-editing tool using a protein language model

• CRISPR-Cas System Classes

  Class 1 (multiple Cas proteins, e.g., Type I, III, IV) and Class 2 (single effector proteins, e.g., Type V)

• OpenCrisper-1 Developer Location

  Berkeley, United States

• Advantage of smaller Cas proteins

  Easier delivery into cells using vehicles like adeno-associated viruses (AAV), leaving space for additional cargo

Timeline

• A study published in Nature surprisingly revealed that some huge phages also have CRISPR-Cas systems, marking the first time a new type of CRISPR-Cas system was found in viral genomes. (Source: Web Search Results)

  2020-02

• UC Berkeley scientists announced the discovery of hypercompact CasΦ (Cas-phi) proteins in megaphages, which are approximately half the size of Cas9 and Cas12, offering advantages for gene editing delivery. (Source: Web Search Results)

  2020-07-20

• Emmanuelle Charpentier and Jennifer Doudna were awarded the Nobel Prize in Chemistry for the development of a method for genome editing, specifically the CRISPR-Cas9 system. (Source: Summary, Wikipedia)

  2020-10-07

• Profluent Bio, a Berkeley-based startup, developed and open-sourced OpenCrisper-1, an AI-driven gene-editing tool that is more effective than existing CRISPR technology. (Source: Summary, Related Documents)

  Unknown

CRISPR

CRISPR (; acronym of clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. Each sequence within an individual prokaryotic CRISPR is derived from a DNA fragment of a bacteriophage that had previously infected the prokaryote or one of its ancestors. These sequences are used to detect and destroy DNA from similar bacteriophages during subsequent infections. Hence these sequences play a key role in the antiviral (i.e. anti-phage) defense system of prokaryotes and provide a form of heritable, acquired immunity. CRISPR is found in approximately 50% of sequenced bacterial genomes and nearly 90% of sequenced archaea. Cas9 (or "CRISPR-associated protein 9") is an enzyme that uses CRISPR sequences as a guide to recognize and open up specific strands of DNA that are complementary to the CRISPR sequence. Cas9 enzymes together with CRISPR sequences form the basis of a technology known as CRISPR-Cas9 that can be used to edit genes within living organisms. This editing process has a wide variety of applications including basic biological research, development of biotechnological products, and treatment of diseases. The development of the CRISPR-Cas9 genome editing technique was recognized by the Nobel Prize in Chemistry in 2020 awarded to Emmanuelle Charpentier and Jennifer Doudna.

Web Search Results

• Megaphages harbor mini-Cas proteins ideal for gene editing

  July 20, 2020 By Robert Sanders | UC Berkeley media relations The DNA-cutting proteins central to CRISPR-Cas9 and related gene-editing tools originally came from bacteria, but a newfound variety of Cas proteins apparently evolved in viruses that infect bacteria. The new Cas proteins were found in the largest known bacteria-infecting viruses, called bacteriophages, and are the most compact working Cas variants yet discovered — half the size of today’s workhorse, Cas9. [...] Smaller and more compact Cas proteins are easier to ferry into cells to do genome editing, since they can be packed into small delivery vehicles, including one of the most popular: a deactivated virus called adeno-associated virus (AAV). Hypercompact Cas proteins also leave space inside AAV for additional cargo.As one of the smallest Cas proteins known to date, the newly discovered CasΦ (Cas-phi) has advantages over current genome-editing tools when they must be delivered into cells to [...] A megaphage (left), a member of a bacteriophage family Biggiephage, injects its DNA — including genes for CasΦ (red) — into bacterial cells to turn the bacteria against the phage’s competitor (top). The reddish Pac-Man-like figures are CasΦ proteins, enzymes that cut up viral DNA. The genome of the bacterium is shown in purple. (UC Berkeley image by Basem Al-Shayeb and Patrick Pausch)

• Mechanisms regulating the CRISPR-Cas systems - Frontiers

  becomes, in a way, an archive of previous infections. Cas proteins are essential for the functioning of the system during each of three distinct phases: adaptation, crRNA maturation and interference.

• Diverse Class 2 CRISPR-Cas Effector Proteins for Genome ...

  Different Cas orthologs may exhibit differences in protein size, which can influence the delivery method of the _cas_ gene. Single effector Cas proteins generally range in size from ~950 to 1400 amino acids. Although different sized enzymes can be used, the smallest functional Cas proteins have been used when there are defined size limits for experiments, such as the ~4.7 kb packaging capacity of adeno-associated viruses (AAVs), a commonly used therapeutic viral vector. Protospacer adjacent [...] CRISPR-Cas systems are most broadly characterized as either class 1 or class 2.24 Class 1 systems require multiple Cas proteins to come together in a complex to mediate interference against foreign genetic elements. Class 1 systems are further divided into three CRISPR-Cas types based on the presence of a specific signature protein: Type I contains Cas3, Type III contains Cas10, and the putative Type IV contains Csf1, a Cas8-like protein (for more information on Class 1 systems, see Koonin _et [...] Type V CRISPR systems encompass all Cas enzymes that have a RuvC-like endonuclease domain with the RNase H fold, conserve catalytic motifs, and lack an HNH nuclease domain.3 Currently there are five such unique single large effector proteins: Cas12a (Cpf1), Cas12b (C2c1), Cas12c (C2c3), Cas12d (CasY), and Cas12e (CasX; Figure 3). Available data of the Cas12 family of proteins suggest that they exhibit several functional similarities but generally show low sequence homology.3

• Discovery of hypercompact CasΦ protein sparks excitement in ...

  Traditionally, the Cas proteins originate from bacteria as a natural immune defence mechanism against bacteriophages. The new variety, CasΦ, evolved in bacteriophages, a group of viruses that infect bacteria. Previously, a study published in Nature in February 2020 surprisingly revealed that some huge phages also have CRISPR-Cas systems by genetically sequencing bacteriophages from diverse ecosystems. The study marks the first time a new type of CRISPR-Cas system is found in viral genomes, [...] Scientists at the University of California, Berkeley recently identified a hypercompact Cas protein, CasΦ (Cas-phi), which measures approximately 70-80-kilodalton, about half the size of Cas9 and Cas12, in a paper published in Science. This marks the discovery of the most compact working Cas variant as of today. [...] CasΦ’s unusual small size is attributed to its limited spacer sequences. In other Cas proteins, spacer sequences functions to store genetic information of viral DNA sequences for potential future targeting. As it is more compact, this means that the gene editing protein can more easily enter a cell through small delivery vehicles, including the most commonly used AAV. It also leaves more space inside the viral vector for additional cargo, such as fusing different proteins to the Cas protein,

• CRISPR Associated Protein - an overview | ScienceDirect Topics

  The CRISPR/Cas (CRISPR-associated proteins) is a microbial adaptive immune system against viruses and plasmids. CRISPR/Cas system uses RNA-guided nucleases to cleave foreign genetic elements (Garneau et al., 2010; Deveau et al., 2010; Makarova et al., 2011; Chylinski et al., 2014). Three main types (I–III) of CRISPR systems have been categorized across a wide range of bacterial and archaeal hosts, based on core elements content and sequences (Makarova et al., 2011). In the type II system,