Successful T cell engineering with gene scissors
The idea of genetically modifying a patient’s own immune cells and deploying them against infections and tumors has been around since the 1980s. But to this day modified T cells are still not as effective as natural T cells and have been only been of limited clinical value. Using the new CRISPR-Cas9 gene editing tool, a team at the Technical University of Munich (TUM) has now engineered T cells that are very similar to physiological immune cells.
There are two forms of T cell therapy: either a recipient receives cells from a donor, or the recipient’s own T cells are removed, genetically reprogrammed in a laboratory and unleashed against an infection or tumor in the body. While the first method has proven to be successful in clinical models, reprogramming T cells is still beset with problems.
The team led by Professor Dirk Busch, Director of the Institute for Medical Microbiology, Immunology and Hygiene at the TUM, has generated modified T cells for the first time that are very similar to their natural counterparts and could solve some of those problems. To do so, they utilized the new CRISPR-Cas9 gene scissors, which can be used to snip out and replace targeted segments of the genome.
Both the conventional methods and the new method target the key homing instrument of T cells, known as the T cell receptor. The receptor, residing on the cell’s surface, recognizes specific antigens associated with pathogens or tumor cells, which the T cell is then able to attack. Each receptor is made up of two molecular chains that are linked together. The genetic information for the chains can be genetically modified to produce new receptors that are able to recognize any desired antigen. In this way, it is possible to reprogram T cells.
Targeted exchange using the CRISPR-Cas9 gene scissors
The problem with conventional methods is that the genetic information for the new receptors is randomly inserted into the genome. This means that T cells are produced with both new and old receptors or with receptors having one old and one new chain. As a result, the cells do not function as effectively as physiological T cells and are also controlled differently. Moreover, there is a danger that the mixed chains could trigger dangerous side effects (Graft-versus-Host Disease, GvHD).
“Using the CRISPR method, we’ve been able to completely replace the natural receptors with new ones, because we’re able to insert them into the very same location in the genome. In addition, we’ve replaced the information for both chains so that there are no longer any mixed receptors,” explains Kilian Schober, who is a lead author of the new study along with his colleague Thomas Müller.
Thomas Müller explains the advantages of the modified T cells: “They’re much more similar to physiological T cells, yet they can be changed flexibly. They’re controlled like physiological cells and have the same structure, but are capable of being genetically modified.“ The scientists have demonstrated in a cell culture model that T cells modified in this way behave nearly exactly like their natural counterparts.
“Another advantage is that the new method allows multiple T cells to be modified simultaneously so that they’re able to recognize different targets and can be used in combination. This is especially interesting for cancer therapy, because tumors are highly heterogeneous,” Dirk Busch adds. In the future, the team plans to investigate the new cells and their properties in preclinical mouse models, an important step in preparing for clinical trials with humans.
Learn more: Successful T cell engineering with gene scissors
The Latest on: CRISPR-Cas9 gene scissors
via Google News
The Latest on: CRISPR-Cas9 gene scissors
- Opinion: CRISPR Cas-9 is forcing evolutionon January 24, 2020 at 12:15 pm
The tool relies on three components: the molecular scissors, a CRISPR-associated (Cas ... Using human embryos sourced from a fertility clinic, Chinese scientists tried to use CRISPR-Cas9 to edit a ...
- CRISPR-Cas9: The era of genome editingon January 24, 2020 at 6:12 am
We take a closer look in this edition of Tech 24. Advertising It's often referred to as "DNA scissors". CRISPR-Cas 9 is a powerful tool that scientists can use to edit DNA and modify gene functions.
- Intellia Therapeutics (NASDAQ:NTLA) Cut to “Sell” at Zacks Investment Researchon January 23, 2020 at 7:36 pm
It believes the CRISPR-Cas9 technology has the potential ... The Cas9 protein acts like a pair of molecular scissors that initiates the natural cellular repair process to knockout, repair or insert a ...
- Disabling viruses with CRISPR scissorson January 23, 2020 at 5:00 am
While CRISPR-Cas9 was used to edit out single bases in one gene, Pappu’s team found a downside to this approach. The edited virus quickly mutated to its original form and started causing disease. Hanu ...
- Drug profiling and gene scissors open new avenues in immunotherapyon January 22, 2020 at 12:05 pm
According to a study published in the Blood journal, drug profiling and the CRISPR-Cas9 gene editing method have opened ... Drug profiling and gene scissors open new avenues in immunotherapy.
- Kill Switch for CRISPR Could Make Gene Editing Saferon January 17, 2020 at 7:04 am
These proteins serve as the rocks to CRISPR’s molecular scissors. And soon, they were popping up everywhere ... Liu studies how a modified CRISPR–Cas9 system can change the expression levels of a gene ...
- Crispr put to the test in first in-body gene editing trialson January 7, 2020 at 3:20 am
FILE — Emily King, a co-op student for virology at Editas Medicine in Cambridge, sets up an experiment to quantify DNA. Editas is among those companies looking to treat patients using Crispr-Cas9 ...
- High-tech method for uniquely targeted gene therapyon December 13, 2019 at 7:59 am
Examples of this are the gene scissors CRISPR / Cas9 and the so-called CAR-T cells that are used to treat various forms of cancer. This type of treatment is often engineered by growing viruses in ...
- Gene-editing scandal: CRISPR Cas9 method does not cause mutations in monkeys, study findson December 11, 2019 at 1:47 am
Professor Su Bing and colleagues at the Kunming Institute of Zoology under the Chinese Academy of Sciences examined rhesus monkeys born from embryos modified by the gene-editing tool CRISPR Cas9 ...
- 'Scissors' component of CRISPR/Cas9 sometimes gets stuckon July 2, 2019 at 2:56 am
In biotech these days, CRISPR/Cas9 is a hot topic ... When Cas9 is acting to block gene activity, Cas9 uses a different RNA guide sequence, which doesn't allow the scissors to cut because of ...
via Bing News