User:Kaw66/sandbox

Article Evaluation:

Cas9

The article has a good flow and stays on topic. It has good neutrality, though it states a few times how Cas9 is now a top tool used for gene editing with no sources to back that up. The citations are used correctly and lead to scholarly articles that support the topic. The talk page brings up the point that there is some overlap between the Cas9 and CRISPR pages because this is a system that goes hand in hand. It is difficult to explain Cas9 without relying on heavy explanation of CRISPR, but may be in the best interest of this page.

Plan:

I plan to add a large section about cancer to the article "CRISPR" under the Biomedicine section. I will add information about research performed with using CRISPR on oncogenes and tumor suppressor genes. Experiments have investigated the manipulation of these genes in vitro and in vivo in mice.

Draft:

CRISPR in Cancer
Cancer is a disease that originates from mutated genes. 140 genes have been found in direct correlation to causing cancer. Many on-going and completed studies have been successful in pinpointing the relationships between specific genes and certain cancers. These genetic connections to cancer make the disease a prime candidate for CRISPR therapy. The two main categories of cancer causing genes include oncogenes and tumor suppressor genes. Mutations of these genes, such as activation of oncogenes and deactivation of tumor suppressor genes, can cause cancerous tumors to grow. Therefore, research has focused on editing these genes using CRISPR technology.

In vitro applications
In a cervical cancer research study, CRISPR was used to knock out E6 and E7 genes that are common to human papillomavirus (HPV) and tumor production. Without these two genes, cancerous cells no longer proliferated. An increase in p53 and p21 tumor suppressor genes also occurred, allowing the cells to further defend against cancer.

CRISPR has also been used in vitro to knock out oncogenes. Kawamura and researchers utilized CRISPR to delete NANOG and NANOGP8 genes that have been known to stimulate tumor growth in cancers such as ovarian cancer, breast cancer, colorectal cancer, and prostate cancer. This experiment determined that affected cells had a 50% less chance of forming spheres, 40-60% less chance of migrating, and an increased drug sensitivity.

In vivo applications
In one study, CRISPR/cas9 stimulated KRAS (a tumor suppressor gene) and knocked out p53 and LKB1 (oncogenes), resulting in genetically engineered mice that imitated lung adenocarcinoma. All mutations were done using a single cas9 vector. Of the CRISPR affected mice, one hundred percent developed lung tumors.

In another laboratory, the tumor suppressor genes Pten and Trp53 were shut down using CRISPR in adult mice, causing each mouse to develop tumors in the liver. This was a faster and more accurate method than the original Genetically Engineered Mouse Model (GEMM) gene editing technique.

These two examples of forming cancer cells in mice are important for research on implementing new cancer therapies and drugs as well as gaining a better understanding of how the disease reacts to different stimulations.

Clinical trials
An ongoing clinical trial beginning in fall of 2016 sponsored by Sichuan University in China is one of the first trials to use CRISPR against cancer in a human patient. The trial is for stage five non-small cell lung cancer. The study is designed to edit PD-1 Knockout T cells. CRISPR will delete the gene that causes a cancer patient’s immune cells to die and the newly engineered cells will be injected back into the patient’s body.

At Hangzhou Cancer Hospital, a study plans to knock out the PD-1 gene in lymphocytes for targeting esophageal cancer and has a completion date of December 2018.

Also in China, Peking University First Hospital is conducting studies involving PD-1 knock out. One study completing in December 2020 will be for treatment of prostate cancer. Another study will be in patients with bladder cancer, finishing in September 2019.

The Chinese PLA General Hospital is currently performing a study utilizing CRISPR to focus on treating Leukemia and Lymphoma.

The United States Food and Drug Administration (FDA) has recently approved some similar clinical trials with CRISPR to move forward in the US.