Daily Archives: January 8, 2015

Wednesday, January 07 11:43:20

Novartis is diving deeper into the world of gene-based medicine by signing deals with two U.S. biotech companies, giving it access to a powerful new genome editing technology.

The tie-ups with unlisted Intellia Therapeutics and Caribou Biosciences show the Swiss drugmaker's confidence in the potential of so-called CRISPR technology, both for making new medicines and as a research tool.

CRISPR, which stands for clustered regularly interspaced short palindromic repeats, allows scientists to edit the genes of selected cells accurately and efficiently. It has created great excitement since emerging two years ago and is being tipped for a Nobel Prize.

While current gene therapy approaches involve adding genes to affected cells, CRISPR opens up the possibility of correcting those cells' faulty genes in the lab before returning them to the patient.

Translating that promise into new treatments will take many years but Novartis' decision to apply the technology in its research labs is an important endorsement, since the company is the world's largest drugmaker by sales.

It is also a sign the Swiss group intends to be at the forefront of the nascent field, after recently establishing a new cell and gene therapies unit within the company.

Mark Fishman, head of the Novartis Institutes for BioMedical Research (NIBR), said genome editing could open a new branch of medicine, leading to cures for diseases caused by faulty genes.

"We have glimpsed the power of CRISPR tools in our scientific programmes in NIBR and it is now time to explore how to safely extend this powerful technology to the clinic," he said.

The deal with Intellia gives Novartis exclusive rights to develop programmes focused on engineered chimeric antigen receptor T-cells (CARTs) and the right to develop a certain number of targets for editing hematopoietic stem cells.

Continue reading here:
Novartis: Gene editing is new frontier

By looking at the expression levels of downstream genes of the regulators in breast cancer, investigators at Dartmouth Hitchcock's Norris Cotton Cancer Center (NCCC), led by Chao Cheng, PhD, have identified a gene signature in E2F4 that is predictive of estrogen receptor positive (ER+) breast cancer. The findings, published in Breast Cancer Research, define a new opportunity for personalizing medicine for women whose Oncotype DX assay results classify them as of "intermediate-risk for recurrence." Until now, there has been no standard of care for those with intermediate risk. Results at NCCC support reclassifying 20-30% of those patients as "high-risk for recurrence," indicating they should receive aggressive follow-up treatment.

"Our data-driven approach to designing an effective prognostic genomic signature for E2F4 activity in ER+ breast cancer patients gave us the essential information to develop what will be a simple clinical test to aid physicians in selecting the most effective treatment regimens for each patient," reported Cheng. "Furthermore, our approach is highly flexible, and because of the widespread essentiality of E2F4 in many types of cancer, it will be of great utility in solving many biomedical questions."

With the goal to design an accurate and quick genomic test to measure the activity levels of the regulators associated with E2F4, Cheng's team looked to the aberrant behavior of transcription factors as a way to track and predict the root cause of all cancers - dysregulated gene expression that leads to uncontrollable cell proliferation, tumor genesis, and ultimately metastases.

The target genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) and researchers compared the regulatory activity score (RAS) of E2F4 in cancer tissues to determine the correlation with activity and patient survival. The prognostic signature for E2F4 was significantly predictive of patient outcome in breast cancer regardless of treatment status and the states of many other clinical and pathological variables.

Cheng explained the translational use of the E2F4 signature, "By developing a flexible, reproducible, and predictive test, we are providing physicians working in many areas of cancer with the information they need to tailor treatment regimens to specific individual patients. This is the essence of personalized medicine: the right treatment for the right patient at the right time."

The team's next steps include evaluating the prognostic potential of E2F4 in additional breast cancer datasets to validate its broad effectiveness, and improving the signature by reducing it to its core component genes.

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The collaborators are all from the Geisel School of Medicine at Dartmouth College and affiliated with Dartmouth's Norris Cotton Cancer Center in Lebanon, NH, USA.

This work was supported by the American Cancer Society Research grant IRG-82-003-270, the Centers of Biomedical Research Excellence (COBRE) grant GM103534, and the Geisel School of Medicine at Dartmouth College.

About Norris Cotton Cancer Center at Dartmouth-Hitchcock

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Dartmouth develops prognostic test for E2F4 in breast cancer