CRISPR이 H5NI 및 인플루엔자와 같은 바이러스를 식별하는 새로운 기술에서 핵심 역할을 할 수 있다

CRISPR은 유전자 편집 이상의 역할을 할 수 있다

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)은 유전공학 도구로 가장 잘 알려져 있으며, 최근에는 겸상 적혈구와 같은 유전 질환을 치료하는 데 사용되고 있습니다. 우리는 이러한 응용 사례들을 우리 기사 “From Blindness to Meat Substitutes: CRISPR Gene-Editing Continues to Produce Promising Results”에서 살펴봅니다.

CRISPR이 유전 도구로서 독특한 점은 정확한 유전 서열을 정밀하게 매칭하고 식별할 수 있는 능력입니다.

이 정확성은 이제 질병 검사를 위해 재활용되고 있으며, 일반적인 PCR 검사보다 사용이 더 간단하고 비용 효율적일 수 있습니다.

Broad Institute, MIT, 그리고 Princeton University의 연구원들이 CRISPR 기술 기반 스트립 테스트 출시를 발표했습니다, 이는 계절성 독감의 두 주요 유형인 인플루엔자 A와 B, 그리고 H1N1 및 H3N2와 같은 계절성 독감 아형을 구별할 수 있습니다.

출처: Broad Institute

작동 원리는 무엇인가?

The technology was first developed in 2020, under the name SHINE (Streamlined Highlighting of Infections to Navigate Epidemics). This was built on top of a previously developed CRISPR-based test method,  SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing). While SHERLOCK was efficient, the multiple steps of the methods increased the risks of errors and erroneous readout.

출처: Nature

The new SHINE method can instead detect viruses with both a paper-based colorimetric readout and an in-tube fluorescent readout. Moreover, the fluorescent readout results can be interpreted in an automated fashion via a companion smartphone application.

왜 중요한가?

PCR testing is expensive and requires specialized equipment. As a result, only a small number of patients are tested (outside of pandemic conditions, of course), usually only the segment of patients visiting a hospital instead of their family doctor.

Antigen testing is often used as an alternative to PCR testing, but it is much less reliable and sensitive.

With correct strain identification with a low bar in terms of costs and complexity, clinicians could, for example, decide whether to use Oseltamivir. This common antiviral is effective for only some strains.

Another application would be helping scientists better monitor an epidemic outbreak through rapid testing in the field.

CRISPR이 이전 방법을 능가한다

The 2024 expansion of SHINE to different flu strains is aiming to replace the currently used method in pathology labs, especially PCR.

Typical diagnostic approaches such as polymerase chain reaction (PCR) require lengthy processing times, trained personnel, specialized equipment, and freezers to store reagents at -80°C, whereas SHINE can be conducted at room temperature in about 90 minutes. Currently, the assay only requires an inexpensive heat block to warm the reaction, and the researchers are working to streamline the process with the goal of returning results in 15 minutes.

Overall, CRISPR-based tests could perform better from a practical and commercial perspective and ultimately replace PCR when it comes to test highly variable viruses like flu and coronaviruses.

다음 대상 바이러스

The upcoming version of the CRISPR-based strip tests will likely be expanded so that they can be used to detect the flu virus and which strain is present and distinguish between viruses with similar symptoms, like coronaviruses and influenza (flu virus).

Another urgent topic is the avian and swine influenza strains. These diseases are wreaking havoc on farming operations. They present serious risks to human health, even with a chance of causing a new pandemic if these viruses adapt from their animal hosts to humans.

Because of the previously demonstrated success with COVID and now flu, it is likely that CRISPR-based tests like SHINE will soon become a lot more common. This will be especially useful for quickly evolving viruses, where keeping track of different strains spread is crucial, a task in which antigen strips are usually performing poorly.

CRISPR 기업

1. Ginkgo Bioworks

The company is producing on-demand organisms for specific applications. These include biomedical applications and plenty of industrial and material sciences programs.

It also has a large biosecurity segment, which was booming during the pandemic.

Ginkgo Bioworks (DNA ) has diversified its applications widely with many research programs and partnerships:

• 칸나비노이드
• mRNA 백신 생산 및 핵산 의약품
• 식품 단백질
• 바이오 비료 생산 in partnership with Bayer
• 장 질환을 위한 프로그래머블 미생물
• 미세플라스틱 생물복원
• 생물보안 및 병원체 탐지
• 폐기물 및 오염 물질 재활용

It makes money by being first paid upfront for the development process and then through royalties on the finished product.

Gingko’s partnerships are constantly expanding, with:

• 노보 노디스크와의 파트너십 확대.
• 일본 무역회사 Sojitz Corporation과의 파트너십.
• 극한 저온 환경에서 얼음을 제어하기 위한 신단백질 개발을 위한 DARPA 자금 지원.
• $331M deal with Pfizer.
• $490M deal with Merck to optimize biologics manufacturing.
• $406M deal with Boehringer Ingelheim for undruggable targets.

Ginkgo Bioworks also partners with all the major agricultural corporations, most of which have some interests in biofuel production and microbiology.  A few of these include Bayer, Cargill, Syngenta, Corteva, ADM, Exacta, and more.

출처: Gingko Bioworks

Gingko’s experience in custom designs of genetic sequences, as well as in biosecurity monitoring makes it a good candidate to benefit from the emergence of new DNA-based testing methods.

So with CRISPR-based tests now having been proven as a viable alternative to PCR tests (a massive market, even out of pandemic conditions), Gingko might be able to leverage its experience and partnership to grab a portion of this emerging market.

2. Editas Medicine, Inc.

Editas was founded by Jennifer Doudna, a discoverer of CRISPR-Cas9. Editas started working with Cas9 but is now focused on a proprietary version of Cas12 that they engineered: AsCas12a.

You can read more about Cas12a’s unique properties in our dedicated article “CRISPR-Cas12a2란 무엇이며 & 왜 중요한가?”.

To resume it shortly, Cas12as is unique because:

• Cas9으로 해결하기 어려운 문제들을 Cas12a로 해결할 수 있습니다.
• 이는 Cas9보다 유전자 편집 성공률을 높입니다.
• Cas12a를 사용하면 한 번에 여러 유전자를 수정할 수 있습니다.

You can also read an overview of all of Jennifer Doudna’s companies in the corresponding article “주목해야 할 Jennifer Doudna 기업들.”

Editas is focused on Sickle Cell Disease (SCD) and beta-thalassemia, CRISPR Therapeutics와 BlueBirdBio 경쟁자에게 최초 치료 승인 경쟁에서 패한 두 질병 (CRSP ).

Nevertheless, Editas owns significant patents on CRISPR-Cas12, which has been used by other researchers at the University of New South Wales, Australia, to develop a COVID-19 strip test (the strip test from the Broad Institute researchers mentioned above used CRISPR-Cas13).

Editas focuses on other CRISPR versions than the “classical” CRISPR-Cas9 might come in handy in entering quickly the CRISPR strip test market and commercializing (with or without partnership) their own version of the strip tests developed by researchers in leading universities.