BRAIN CRISPR
© BRAIN Biotech

We CRISPR for You

With our own CRISPR-Cas genome scissors, we meet customer project goals faster and cheaper

Genome editing using CRISPR-Cas (Cas9, Cas12 or others) has revolutionized a long-standing process in nature: that of natural selection, i.e. the successful reproduction of those organisms that are best adapted to their environmental conditions. With CRISPR-Cas technology, not only can the selection process be accelerated enormously; above all, it can be targeted and precise. Molecular biologists can use it to selectively insert, remove or modify individual DNA segments in living organisms.

Why a proprietary development?

In basic research, CRISPR-Cas technology is already being used in a wide range of applications. However, the unclear patent situation specifically for the CRISPR/Cas9 system often prevents its use in companies, due to unforeseeable patent risks and the expensive licensing fees to be paid. For this reason, we have developed BRAIN Engineered Cas (BEC) nuclease, our own variant of the CRISPR-Cas scissors, e.g. to optimize the metabolic performance of microbial production strains within a short time. BEC is a non-Cas9 and non-Cpf1 type genome editing nuclease.


Contact our expert
Dr. Michael Krohn, BRAIN AG

Dr. Michael Krohn

is our expert and business contact in the field of CRISPR

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Chronological development and type of targeted genome modifications: Targeted genome modifications can be achieved using rare cleaving nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), meganucleases (mns, also termed homing endonucleases); MegaTals as fusions of meganucleases and Talens; and clustered, regularly interspaced, short palindromic repeat (CRISPR) RNA-guided nucleases.

The path to BRAIN-Engineered-Cas (BEC) nuclease

To identify and develop the novel BEC nuclease, we used metagenome sequencing and protein engineering techniques. Thus, we have developed a novel CRISPR-associated class 2 nuclease that exhibits low sequence homology compared to other CRISPR nucleases and targets DNA with a unique molecular mechanism.

A patent protecting the nuclease DNA sequence has been filed and we expect to be able to use this system freely in the future ("freedom to operate").


#1
Let's start with nature

Metagenomics samples were selected using rational bioprospecting and the DNA of all microorganism living in those habitats was isolated.

#2
Metagenomics meets Bioinformatics

The isolated DNA was sequenced using state of the art next generation sequencing techniques and analyzed to identify novel genome editing tools.

#3
Shaping the heroes

The selected metagenomics sequences were optimized by protein engineering to enhance the genome editing activity and specificity and one best performing prime candidate was selected (BEC).

#4
BEC comes into action

To perform genome editing, the BEC protein loaded with a specific gRNA is introduced into the target cell.

#5
Select the target

With the help of a specific spacer sequences incorporated inside the gRNA the BEC protein can be programmed to find and bind a specific region on the genome of the target cell.

#6
Processing the DNA

If the programmed spacer sequence perfectly matches the DNA sequence present in the genome the BEC protein precisely cuts the DNA at the predefined position.

#7
Gene knock-out

The native repair mechanism of the target cell repairs the DNA that was targeted by the BEC protein in a non-prefect way leading to small insertions or deletions inside the genome. This mechanism can be used to knock-out genes.

#8
Gene knock-in

The targeted DNA can be repaired by the integration of a repair fragment that researchers can design to precisely integrate genes of interest into the genome.

#9
Optimized organism

The BEC protein can be used to specifically knock-out or knock-in genes to optimize the genome of a variety of organisms.

Application areas

Our novel CRISPR-associated nuclease has been validated both internally and externally with partners and has demonstrated DNA targeting activity in selected bacteria, fungi and yeasts. Accordingly, the technology is ready for use in developments based on these organisms. Activity in plants has also been demonstrated, but validation is pending. Genome editing tests for other application areas such as mammalian cell lines are currently ongoing (as of July 2021).

We are already successfully using BEC not only in our own projects, but also in customer projects.

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We’re looking for partners for detailed screening of as yet unpatented candidates

As part of the development of BEC, we have additionally identified approximately 2,000 previously unused class 2 CRISPR nucleases that could be used for genome editing. With a focused investment scope in mind, we have analyzed a limited number in detail so far and have already filed for initial IP protection for 15 further nucleases.

We are already engaged in discussions with potential partners and are open to further partnerships to accelerate the detailed screening of promising CRISPR nuclease candidates that have not yet been patented.

Find our proposal for a partnership in the paper below:


Teaser

Alternative & Novel CRISPR Cas System

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Read the related article in News & Views:


21 May 2021
CRISPR process

An Alternative CRISPR-Cas Tool for Genome Editing

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