CRISPR을 암 치료에 어떻게 활용할 수 있을까

CRISPR 유전 질환을 넘어

When CRISPR-Cas9 was first found and subsequently earned its discoverers a Nobel Price in 2020, the obvious first application of this technology was gene therapy. This is because CRISPR allows for very precise and targeted gene editing, making possible the idea of correcting abnormal gene sequences in patients.

하지만 CRISPR의 또 다른 성장 잠재력은 종양학(암 치료) 분야에 있으며, 현재 진행 중인 유전자 편집 임상 시험 중 가장 많은 수를 차지하고 있습니다.

출처: ARK Invest

CRISPR가 암 연구에 처음 적용된 사례 중 하나는 기존의 유전 변형 도구들을 대체하는 것이었습니다. CRISPR는 비용이 저렴하고, 속도가 빠르며, 사용이 간편해 연구자들이 마우스와 같은 유전적으로 변형된 동물 모델을 더 많이 활용할 수 있게 되었습니다.

하지만 연구자들을 위한 도구로서의 CRISPR는 시작에 불과하며, 암에 맞서는 무기로 발전할 가능성을 가지고 있습니다.

CRISPR로 암을 치료할 수 있을까?

The main obstacle on the way to cure cancer is that this is not just one disease. Each cancer is made of abnormal cells in its own unique way. This means that no chemical drug is likely to work on every cancer, as each will have a unique pattern of resistance and weaknesses.

유망한 전략 중 하나는 환자에게서 면역 세포를 추출한 뒤 이를 변형시켜 암 세포를 공격하도록 만드는 것입니다. 변형된 세포는 실험실에서 증식된 뒤 환자에게 다시 주입됩니다.

출처: Cancer.gov

이것이 바로 유망한 CAR‑T 암 치료법(키메라 항원 수용체)의 기본 원리입니다.

다른 유사한 방법들은 T 림프구 대신 NK 림프구(자연 살해 세포)를 이용합니다. 어느 경우든 CRISPR는 세포가 환자 몸에 의해 거부되지 않도록 개선하고, 암을 찾고 파괴하는 효율을 높이는 데 사용됩니다.

가장 진보된 치료법은 대량 배양이 가능하면서도 여러 환자에게서 받아들여지는 CAR‑T 또는 CAR‑NK 세포를 설계하는 것입니다.

CRISPR 암 치료를 선도하는 기업

1. CRISPR Therapeutics

CRSP 가격 차트

One of the leading companies in this sector is CRISPR Therapeutics (CRSP ), founded by one of the discoverers of CRISPR-CAs9.

이 회사의 CAR‑T 세포는 암 세포를 표적으로 할 뿐만 아니라 원치 않는 부작용(이식편대숙주병)의 위험을 줄이고, 변형된 면역 세포가 환자 몸 안에서 더 오래 살아남아 암 세포를 공격할 수 있도록 생존 시간을 연장하도록 설계되었습니다.

출처: CRISPR Therapeutics

The company currently has 7 candidates in the pipeline, of which 4 already in clinical trials.

CRISPR은 또한 Nkarta Therapeutics(NKTX)와 협력하여 전임상 단계에 있는 CAR‑NK 치료제에 투자하고 있습니다. CAR‑NK 치료제는 부작용 발생 가능성이 더 낮고 고형 종양(성인 암의 90%)에 대해 더 효과적일 잠재력을 가지고 있습니다.

2. Ginkgo Bioworks Holdings, Inc.

DNA 가격 차트

Synthetic biology company Gingko Bioworks announced in 2023년 4월 a partnership with the Wisconsin Alumni Research Foundation (WARF) to jointly develop the new generation of CAR‑T treatment. Researchers at the WARF were behind the first FDA‑approved CAR‑T therapy. Today, 6 CAR‑T therapies have been approved, and intense research efforts are being made to adapt CAR‑T therapies to solid tumors.

A key technology behind Bioworks’ ambitions in CAR‑T therapies is its CAR‑T screening platform. It allows it to “scan” hundreds of thousands of CAR‑T designs, helping find quicker and cheaper what might work for solid tumors.

2. Editas Medicine, Inc.

EDIT 가격 차트

Editas is another gene‑editing biotech company with programs targeting cancer. It currently has 2 different strategies in oncology, both relying on genetically modifying immune T‑cells.

출처: Editas

Its autologous CAR‑T cell therapies are developed in partnership with Bristol Myers Squibb (BMY).

It also has a program running with Immatix (IMTX) on a proprietary Activated allogeneic cell therapy (ACT), a therapy modifying the tumor micro‑chemical environment in order to reduce its resistance or growth.

Editas is focused on using a variant of CRISPR called AsCas12a. This is expected to create more precise and efficient gene editing.

(We explained in more detail the potential of Cas12a in a dedicated article, “What Is CRISPR-Cas12a2? & Why Does It Matter?”)

4. Caribou Biosciences

CRBU 가격 차트

Caribou Biosciences (CRBU ) is working on CAR‑T therapies for blood cancers, with 2 out of 3 candidates in phase I of clinical trials.  It has a CAR‑NK therapy platform in the pre‑clinical stage to target solid tumors.

It also has a partnership with AbbVie (ABBV ) for cancer cell therapies (CAR‑T) at an undisclosed stage due to confidentiality agreements.

출처: Caribou

Caribou is also pushing the frontier of CRISPR technology with the invention of a DNA/RNA hybrid CRISPR system, ChRDNA.

This system should be able to achieve a strong reduction of off‑target gene editing, a constant concern for all gene editing and CRISPR therapies. This, in turn, should reduce side effects potential dangers for the patients and, increase efficiency, and maybe allow for smaller doses.

5. Intellia Therapeutics, Inc.

NTLA 가격 차트

Intellia is the first company to achieve successful systemic CRISPR gene editing in humans. This is especially useful for genetic diseases where ex‑vivo, like CAR‑T therapies, might not be an option. The company still favors an ex‑vivo approach for its cancer therapies.

출처: Intellia

Intellia’s main focus is rare diseases, with a total of 8 candidates, of which 2 are in early clinical stage. In the cancer segment, one is at the pre‑clinical stage, and another one is at the IND‑enabling stage (Investigational New Drug).

While the Itellia cancer pipeline is interesting, investors will want to pay attention to the rare disease portfolio, likely the focus of markets for the foreseeable future.