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GEG Tech’s mission is to design and provide cutting-edge vectorization and gene editing solutions, to help private and public research laboratories meet their innovation challenges.

15/10/2021

The application of nanomaterials in the diagnosis, prevention, and treatment of viral diseases is reviewed in detail, highlighting areas of significant progress or stagnation from the past few decades.

Wilm's tumor antigen (WT1) is a protein overexpressed in AML and many other tumor types and has become an attractive tar...
14/10/2021

Wilm's tumor antigen (WT1) is a protein overexpressed in AML and many other tumor types and has become an attractive target for immunotherapy-based approaches to cancer treatment. AML is the most common type of acute leukemia in adults and progresses rapidly to a fatal stage without treatment. NTLA-5001 is being developed using patient-derived T cells, in which the patient's own TCR is replaced by a natural (i.e., from a healthy donor) TCR of high avidity with specificity for WT1. Complete elimination of the endogenous TCR is achieved by CRISPR-Cas9-mediated replacement of the TRAC locus with the WT1 TCR and site-specific knockout of the TRBC locus, which encodes for T-cell receptor beta chains. The CRISPR-Cas9 reagents are delivered to T cells via an adeno-associated virus (AAV) vector. Intellia Therapeutics announced that it had received IND approval from the FDA for NTLA-5001, which is an autologous T-cell receptor (TCR)-T therapy candidate for acute myeloid leukemia (AML).NTLA-5001 is Intellia's first ex vivo CRISPR therapy candidate for cancer to approach the clinic, and screening of patients for enrollment in the Phase 1/2a trial is expected to begin by the end of this year.

In this week’s clinical update, we take a look at a CRISPR-engineered T cell receptor-T cell therapy that is designed to treat all genetic subtypes of acute myeloid leukaemia.

Brain metastases from breast cancer develop in patients with metastatic breast cancer. Current treatment options for bra...
11/10/2021

Brain metastases from breast cancer develop in patients with metastatic breast cancer. Current treatment options for brain metastases include surgery, radiation, chemotherapy and targeted therapies, but these have limited success and may worsen neurological function. Because 80% of women with brain metastases from breast cancer die within a year of diagnosis, Cittelly and her team want to find a way to target cancer cells after they have spread to the brain.
Working with cells in the lab, they have identified the interleukin 13 receptor alpha 2 (IL13Ra2) as a likely target for treatment. This is a protein that is found at increased levels in cancer cells that metastasize to other locations in the body, particularly the brain and lungs. In addition, the protein has shown vulnerability to treatment with CAR T cells in clinical trials of brain tumors. The researchers' next step is to initiate a collaboration with CAR T cell experts to better understand how CAR T cell therapy might target IL13Ra2.
Ultimately, Cittelly hopes to see clinical trials for patients with breast cancer that has metastasized to the brain, as they are currently excluded from clinical trials.

Breast cancer patients whose cancer spreads to the brain may soon have new treatment options, thanks to research led by CU Cancer Center member Diana Cittelly, PhD.

According to Jing Pan's article in the Journal of Clinical Oncology titled: Donor-derived CD7 chimeric antigen receptor ...
07/10/2021

According to Jing Pan's article in the Journal of Clinical Oncology titled: Donor-derived CD7 chimeric antigen receptor T cells for T-cell acute lymphoblastic leukemia: first-in-human phase I trial, CAR T cells are reported to be remarkably effective in patients with B-cell acute lymphoblastic leukemia (ALL) but have not been successful to date in patients with T-cell ALL (T-ALL). Now, data from Pan and colleagues demonstrate the safety and impressive short-term efficacy of allogeneic donor-derived anti-CD7 CAR T cells in an early phase clinical trial involving patients with relapsed and/or refractory T-ALL.

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HIV attacks the immune system by infecting a type of white blood cell in the body that is vital for fighting infection. ...
06/10/2021

HIV attacks the immune system by infecting a type of white blood cell in the body that is vital for fighting infection. Without treatment, HIV can destroy these white blood cells, reducing the body's ability to develop an immune response, eventually leading to AIDS. Kevin Morris, Ph.D., of City of Hope and the Menzies Health Institute Queensland at Griffith University in Australia, has been investigating a new approach to blocking and locking down HIV in mice. The researchers are using exosomes, tiny nanoparticles capable of being taken up by cells, to deliver a new recombinant anti-HIV protein, called ZPAMt, into HIV-infected cells. The ZPAMt protein was designed by researchers to bind to a region of the virus called the LTR that is essential for virus replication. The protein contains an epigenetic marker that alters the way HIV genetic information is expressed, suppressing it and rendering the virus unable to divide and multiply.
Exosomes are able to cross the blood-brain barrier and enter the brain, making this treatment capable of targeting this hard-to-reach organ. In the future, researchers plan to study the use of exosomes to deliver treatments that can help anti-HIV CAR T cells kill HIV-infected cells.

BigField GEG Tech's insight: HIV attacks the immune system by infecting a type of white blood cell in the body that is vital for fighting infection. Without treatment, HIV can destroy these white blood cells, reducing the body's ability to develop an immune response, eventually leading to AIDS. K...

Since CRISPR-Cas was first adapted for eukaryotic genome editing in 2013, the technology and the toolbox have advanced b...
04/10/2021

Since CRISPR-Cas was first adapted for eukaryotic genome editing in 2013, the technology and the toolbox have advanced by leaps and bounds. Today, a number of CRISPR-based therapies are moving through clinical trials with promising results. Despite these improvements, a number of challenges remain in the field of CRISPR medicine, one of which is the challenge associated with the limited size capacity of adeno-associated viral (AAV) vectors used to deliver gene editing reagents to cells. Last year, the CasΦ family of CRISPR endonucleases (also known as Cas12j) was discovered as a very compact CRISPR system in ancient giant phages. In addition, CasΦ was shown to edit genomic DNA in mammalian and plant cells, but questions about its mechanism of action remained open. Thus, this discovery raised hopes that a solution to the AAV capacity challenge was at hand. Only a year later, Guillermo Montoya's team at the University of Copenhagen, Denmark, answered these questions by solving, using Cryo-em, the structure of
Cas12j3 in complex with a DNA target after cleavage, paving the way for future optimization of CasΦ genome editors and facilitating the future redesign of this CRISPR system for therapeutic genome editing.

BigField GEG Tech's insight: Since CRISPR-Cas was first adapted for eukaryotic genome editing in 2013, the technology and the toolbox have advanced by leaps and bounds. Today, a number of CRISPR-based therapies are moving through clinical trials with promising results. Despite these improvements,...

Editas Medicine said today its lead candidate EDIT-101, an in vivo CRISPR gene editing treatment for Leber congenital am...
01/10/2021

Editas Medicine said today its lead candidate EDIT-101, an in vivo CRISPR gene editing treatment for Leber congenital amaurosis-10 (LCA10), showed positive initial clinical data showing it to be safe, and to have generated "signals" of efficacy in two of three patients in the study’s adult mid-dose cohort.

BigField GEG Tech's insight: Editas Medicine said today its lead candidate EDIT-101, an in vivo CRISPR gene editing treatment for Leber congenital amaurosis-10 (LCA10), showed positive initial clinical data showing it to be safe, and to have generated "signals" of efficacy in two of three patient...

Tumor suppressor genes block cell growth, preventing cancer cells from spreading. Scientists believe that mutations in t...
30/09/2021

Tumor suppressor genes block cell growth, preventing cancer cells from spreading. Scientists believe that mutations in these genes allow tumors to flourish unchecked. Now, Howard Hughes Medical Institute researcher Stephen Elledge's team has discovered a surprising new action for many of these faulty genes. Elledge had a hunch that defective tumor suppressor genes were doing something more than speeding up tumor cell growth. From a list of 7,500 genes, her team used CRISPR to engineer thousands of tumor cells. Each was missing a functional version of one of these genes. The researchers placed the cells in two types of mice: those with an immune system and those without. Then the team studied the tumors that developed. Elledge's method revealed the many different genes that tumors can mutate to evade the body's defenses. To explore the possible mechanisms triggered by the mutations, the researchers focused on a gene called GNA13. The gene's mutation protects cancer cells from the immune system's T cells, creating a safe space for the tumor to grow.
According to the study, more than 100 mutated tumor suppressor genes can prevent the immune system from identifying and destroying malignant cells in mice.

During tumorigenesis, tumors must evolve to evade the immune system and do so by disrupting the genes involved in antigen processing and presentation or up-regulating inhibitory immune checkpoint

Over the past seven years, researchers at Temple University's Lewis Katz School of Medicine have been developing and ref...
28/09/2021

Over the past seven years, researchers at Temple University's Lewis Katz School of Medicine have been developing and refining a CRISPR-based gene-editing technology for the treatment of human immunodeficiency virus type 1 infection, also known as HIV. From this effort has emerged a potentially revolutionary therapy known as EBT-101, which, with its recent acceptance as an Investigational New Drug (IND) by the U.S. Food and Drug Administration, could become the first functional cure for chronic HIV infection. In preclinical studies, EBT-101 has been shown to effectively excise HIV proviral DNA from the genomes of various cells and tissues, including HIV-infected human cells and humanized mouse cells and tissues. The new IND approval for EBT-101 paves the way for the first Phase 1/2 clinical trials of a CRISPR-based therapy for HIV infection. The clinical trials will be initiated and managed by Excision BioTherapeutics, Inc. which has been a major collaborator with Temple on the development of CRISPR-based systems for HIV treatment.

For the last seven years, researchers at the Lewis Katz School of Medicine at Temple University have been developing and refining CRISPR-based gene-editing technology for the treatment of human immunodeficiency virus type 1 (HIV) infection.

Poseida Therapeutics, a San Diego-based clinical-stage biopharmaceutical company, has received FDA approval for an inves...
24/09/2021

Poseida Therapeutics, a San Diego-based clinical-stage biopharmaceutical company, has received FDA approval for an investigational new drug: its first allogeneic CAR-T candidate for the treatment of relapsed or refractory multiple myeloma. The new candidate, called P-BCMA-ALLO1, is designed to target the B cell maturation antigen (BCMA), which is primarily expressed by plasma cells and certain mature B cells. P-BCMA-ALLO1 is being developed using Poseida's piggyBac®, a genetic element that "cuts and pastes" or transposes DNA between vectors and chromosomes but also the hybrid Cas-CLOVER™ site-specific gene editing system that combines the use of an enzymatically inactivated Cas9 endonuclease fused to Poseida's proprietary dimeric nuclease, Clo051. Poseida Therapeutics plans to dose the first patients with P-BCMA-ALLO1 later this year.

This week’s update looks at P-BCMA-ALLO1, a Cas-CLOVER-edited allogeneic CAR-T candidate that is being developed for the treatment of multiple myeloma.

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