The birth of gene therapy as a therapeutic avenue began with the repurposing of viruses for transgene delivery to patients with genetic diseases.

Gene therapy enjoyed an initial phase of excitement, until the recognition of immediate and delayed adverse effects resulted in death and caused a major setback. More recently, the discovery and development of CRISPR/cas9 has re-opened a door for gene therapy and changed the way scientists can approach a genetic aberration—by fixing a non-functional gene rather than replacing it entirely, or by disrupting an aberrant pathogenic gene.

CRISPR/cas9 provides extensive opportunities for programmable gene editing and can become a powerful asset for modern medicine. Genome or gene editing holds the keys to correct a variety of diseases and defects.

Discovery of the clustered regularly-interspaced short palindromic repeats (CRISPR), the mechanism of the CRISPR-based prokaryotic adaptive immune system (CRISPR-associated system, CAS) – and its repurposing into a potent gene editing tool has revolutionized the field of molecular biology and generated excitement for new and improved gene therapies. There are a group of technologies that provide the scientists an ability to alter an organism’s DNA – basically adding, removing or altering the genome at particular locations.

Why we should be interested in CRISPR-Cas9

The CRISPR-Cas9 gene-editing system has the potential to alter the way life sciences researchers edit and engineer the DNA of virtually any living thing on the face of the earth.

It gives a deeper understanding of the way genes function in cells and the development of new and more effective medical treatments and therapies for a range of devastating diseases.

By removing the underlying dysfunctional DNA sequences, it could be possible not only to cure these diseases but to ensure these conditions no longer pass to the next generation.

Its application in agriculture and industry also promises the development of more robust, disease-resistant plants and animals.

The potential benefits are HUGE

Genome engineering – Understanding CRISPR-Cas9 system

What is “CRISPR”?

Clustered Regularly Interspaced Short Palindromic Repeats are the hallmark of a bacterial defense system that forms the basis for CRISPR-Cas9 genome editing technology. In genome engineering, the term “CRISPR” or “CRISPR-Cas9” is often used referring to various CRISPR-Cas9 and -CPF1 and other systems that can be programmed to target specific stretches of genetic code and to edit DNA at precise locations, as well as for other purposes, such as for new diagnostic tools. researchers can permanently modify genes in living cells and organisms and, in the future, may make it possible to correct mutations at precise locations in the human genome in order to treat genetic causes of disease. Other systems are now available, such as CRISPR-Cas13’s, that target RNA, providing alternate avenues for use and with unique characteristics that have been leveraged for sensitive diagnostic tools, such as SHERLOCK.

Where do CRISPR’s come from?

CRISPRs were first discovered in archaea (and later in bacteria) by Francisco Mojica, a scientist at the University of Alicante in Spain. He proposed that CRISPRs serve as part of the bacterial immune system, defending against invading viruses. They consist of repeating sequences of genetic code, interrupted by “spacer” sequences – remnants of genetic code from past invaders. The system serves as a genetic memory that helps the cell detect and destroy invaders (called “bacteriophage”) when they return.

Genome engineering – Understanding CRISPR-Cas9 system

How does the system work?

CRISPR “spacer” sequences are transcribed into short RNA sequences (“CRISPR RNAs” or “crRNAs”) capable of guiding the system to matching sequences of DNA. When the target DNA is found, Cas9 – one of the enzymes produced by the CRISPR system – binds to the DNA and cuts it, shutting the targeted gene off. Using modified versions of Cas9, researchers can activate gene expression instead of cutting the DNA. These techniques allow researchers to study the gene’s function. Research also suggests that CRISPR-Cas9 can be used to target and modify “typos” in the three-billion-letter sequence of the human genome in an effort to treat genetic disease.

How does CRISPR-Cas9 compare to other genome editing tools?

It is proving to be an effective and more customizable alternative, since the CRISPR-Cas9 system itself is capable of cutting DNA strands, CRISPRs do not need to be paired with separate cleaving enzymes as other tools do. They can also easily be matched with tailor-made “guide” RNA (gRNA) sequences designed to lead them to their DNA targets. They can also be used to target multiple genes simultaneously, which is another advantage that sets it apart from other gene-editing tools. Thousands of gRNA sequences have been already created and are now available to the research community.

How does CRISPR-Cpf1 differ from CRISPR-Cas9?

The DNA-cutting enzyme Cas9 forms a complex with two small RNAs, both of which are required for the cutting activity. The Cpf1 system is simpler in that it requires only a single RNA. The Cpf1 enzyme is also smaller than the standard SpCas9, making it easier to deliver into cells and tissues. Cpf1 cuts DNA in a different manner than Cas9. When the Cas9 complex cuts DNA, it cuts both strands at the same place, leaving ‘blunt ends’ that often undergo mutations as they are rejoined. With the Cpf1 complex the cuts in the two strands are offset, leaving short overhangs on the exposed ends. This is expected to help with precise insertion, allowing researchers to integrate a piece of DNA more efficiently and accurately. Cpf1 cuts far away from the recognition site, meaning that even if the targeted gene becomes mutated at the cut site, it can likely still be re-cut, allowing multiple opportunities for correct editing to occur. Cpf1 system provides new flexibility in choosing target sites. Like Cas9, the Cpf1 complex must first attach to a short sequence known as a PAM, and targets must be chosen that are adjacent to naturally occurring PAM sequences. The Cpf1 complex recognizes very different PAM sequences from those of Cas9. This could be an advantage in targeting, for example, the malaria parasite genome and even the human genome.

What other scientific uses might CRISPR have beyond genome editing?

Besides creating cell and animal models can be used to accelerate research into diseases such as cancer and mental illnesses. It is now also being developed to be used as a rapid diagnostic.

For further information on the latest breakthroughs, developments & trends on CRISPR and its associated approaches to Genome editing, please feel free to write to us at: info@effectualservices.com

Effectual’s CRISPR research framework is a deep dive into this ecosystem and shall help you understand the intricacies of this nascent innovative domain with insights backed with credible data sources.

Why Effectual – CRISPR & IP - A CRISPR Ecosystem Research Framework

Overall Intellectual Property Landscape

We can provide you an in-depth review of the various patents and affiliated IP documents that have been published related to the diverse technologies, methods and compositions associated with the use of CRISPR, covering both historical and recent trends in R&D.

Relevant Prior Art Search

IP literature, shortlisting key words and phrases that have been used to describe CRISPR and associated technologies – including information on historical use of terms across different types of IP filings, key affiliated terms, to further identify similar innovations & other related trends.

Patent Valuation Analysis

A competitive benchmarking and valuation analysis of IP documents published in this field of innovation, taking into consideration important parameters, such as type of IP document, year of application, time to expiry, number of citations and jurisdiction.

Patentability & Freedom to Operate

A systematic approach to identify relevant areas of innovation by analyzing published IP documents, defining the uniqueness of patented / patent pending innovations, understanding the scope of patentability in this domain, and pinpointing jurisdictions where new and / or modified claims may be filed without infringing on existing IP.

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Research on patent applications that were filed across different jurisdictions and their relative value in the IP ecosystem, segregating the intellectual capital, in terms of area of innovation, offering means to understand key areas of research and identify innovation-specific IP filing trends. A summary of granted patents across different jurisdictions and their relative value in the IP ecosystem. Segregating granted patents into relevant categories in order to develop a more detailed perspective on the diverse types of innovations in this domain and the feasibility for innovators to enter into promising product markets.

Pockets of Innovation, White Spaces & Claims Analysis

An insightful analysis of the various CPC codes used in published IP literature and their affiliated families, in order to identify historical and existing pockets of innovation, based on the functional area & industry described by the elaborate and systematic system of classifying IP, while featuring a discussion on prevalent white spaces (based on CPC symbols).

We can help you analyze and summarize key inferences from the independent claims mentioned in granted, active patents in the dataset, using a systematic segregation approach