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Archive for the ‘CRISPR/Cas9 & Gene Editing’ Category


Human gene editing continues to hold a major fascination within a biomedical and biopharmaceutical industries. It’s extraordinary potential is now being realized but important questions as to who will be the beneficiaries of such breakthrough technologies remained to be answered. The session will discuss whether gene editing technologies can alleviate some of the most challenging unmet medical needs. We will discuss how research advances often never reach minority communities and how diverse patient populations will gain access to such breakthrough technologies. It is widely recognize that there are patient voids in the population and we will explore how community health centers might fill this void to ensure that state-of-the-art technologies can reach the forgotten patient groups . We also will touch ethical questions surrounding germline editing and how such research and development could impact the community at large.

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CRISPR cuts turn gels into biological watchdogs

Reporter: Irina Robu, PhD

Genome editing if of significant interest in the prevention and treatment of human diseases including single-gene disorders such as cystic fibrosis, hemophilia and sickle cell disease. It also shows great promise for the prevention and treatment of diseases such as cancer, heart disease, mental illness and human immunodeficiency virus infection. However, ethical concerns arise when genome editing, using technologies such as CRISPR-Cas9 is used to alter human genomes.

James Collins, bioengineer at MIT and his team worked with water-filled polymers that are held together by strands of DNA, known as DNA hydrogels. To alter the properties of these materials, these scientists turned to a form of CRISPR that uses a DNA-snipping enzyme called Cas12a, which can be programed to recognize a specific DNA sequence. The enzyme then cuts its target DNA strand, then severs single strands of DNA nearby. This property lets scientists to build a series of CRISPR-controlled hydrogels encapsulating a target DNA sequence and single strands of DNA, which break up after Cas12a identifies the target sequence in a stimulus. The break-up of the single DNA strands activates the hydrogels to change shape or completely dissolve, releasing a payload.

According to Collins and his team, the programmed hydrogels will release enzymes, small molecules and human cells as part of a smart therapy in response to stimuli. However, in order to make it a smart therapeutic, the researchers in collaboration with Dan Luo, bioengineer at Cornell University placed the CRISPR- controlled hydrogels into electric circuits. The circuit is switched off in response to the detection of the genetic material of harmful pathogens such as Ebola virus and methicillin-resistant Staphylococcus aureus. The team used these hydrogels to develop a prototype diagnostic tool that sends a wireless signal to identify Ebola in lab samples.

Yet, it is evident that these CRISPR-controlled hydrogels show great potential for the prevention and treatment of diseases.

SOURCE

https://www.nature.com/articles/d41586-019-02542-3?utm_source=Nature+Briefing

 

 

 

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At Technical University of Munich (TUM) Successful Genetical modification of a patient’s own immune cells, T cell receptors, using CRISPR-Cas9 gene editing tool. The engineered T cells are very similar to the physiological immune cells.

Reporter: Aviva Lev-Ari, PhD, RN

 

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.

Near-natural properties

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.

Original Publication

Kilian Schober, Thomas R. Müller, Füsun Gökmen, Simon Grassmann, Manuel Effenberger, Mateusz Poltorak, Christian Stemberger, Kathrin Schumann, Theodore L. Roth, Alexander Marson and Dirk H. Busch: Orthotopic replacement of T-cell receptor ɑ- and β-chains with preservation of near-physiological, Nature Biomedical Engineering, June 12, 2019, DOI: 10.1038/s41551-019-0409-0

 

SOURCE

https://www.tum.de/nc/en/about-tum/news/press-releases/details/35560/

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@BroadInstitute a shift from Permanently editing DNA to Temporarily revising RNA – An approach with promise for addressing the risk of developing Alzheimer’s by deactivating APOE4 – RESCUE: RNA Editing for Specific C to U Exchange, the platform builds on REPAIR: RNA Editing for Programmable A to I

Reporter: Aviva Lev-Ari, PhD, RN

 

  • The RNA editors converted “the nucleotide base adenine to inosine, or letters A to I. Zhang and colleagues took the REPAIR fusion and evolved it in the lab until it could change cytosine to uridine, or C to U.”
  • Using Cas13, Zhang’s team was able to take the APOE4 gene — believed to carry the added risk of spurring Alzheimer’s — and changed it to a benign APOE2.

RNA-guided DNA insertion with CRISPR-associated transposases

Science  05 Jul 2019:
Vol. 365, Issue 6448, pp. 48-53
DOI: 10.1126/science.aax9181
SOURCE

Other related articles on CRISPR derived Gene Editing for Gene Therapy published in this Open Access on Online Scientific Journal include the following:

 

Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology

Forthcoming 12/2019, Volume Two

by

Prof. Marcus W. Feldman, PhD, Editor, Stanford University

Prof. Stephen J. Williams, PhD, Editor, Temple University

and Aviva Lev-Ari, PhD, RN, Editor, LPBI Group 

 

Part 2: CRISPR for Gene Editing and DNA Repair

2.1 The Science – 77 articles

2.2 Technologies and Methodologies – 27 articles

2.3 Clinical Aspects – 9 articles

2.4 Business and Legal – 18 articles

 

Series B: Frontiers in Genomics Research

 

  • VOLUME 1: Genomics Orientations for Personalized Medicine. On Amazon.com since 11/23/2015

http://www.amazon.com/dp/B018DHBUO6

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FIVE Forthcoming Books on CRISPR in 2019-2020: Flooded market or CRISPR-fatigued readers – Not to Worry !!!!!

Author: Aviva Lev-Ari, PhD, RN

 

From: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Date: Thursday, July 4, 2019 at 8:39 PM

To: <damian.garde@statnews.com>

Cc: Marcus W Feldman <mfeldman@stanford.edu>, “Stephen Williams, PhD” <sjwilliamspa@comcast.net>, Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>, Gail Thornton <gailsthornton@yahoo.com>

Subject: Regarding your article: Walter Isaacson is writing a book about CRISPR. He’s got company —>>>>>> e-mail from AVIVA LEV-ARI, PhD, RN, EDITOR-in-CHIEF PharmaceuticalIntelligence.com

attn:

damian.garde@statnews.com

 

Dear Mr. Grade,

 

In your article

Walter Isaacson is writing a book about CRISPR. He’s got company

By DAMIAN GARDE @damiangarde 7/2/2019

https://www.statnews.com/2019/07/02/walter-isaacson-crispr-books/?utm_source=STAT+Newsletters

 

you mention the following FOUR forthcoming books on CRISPR:

 

  • Walter Isaacson, the famed biographer, is among a number of authors working on books about gene editing and CRISPR.

Title TBD, Year of Publication and Publisher, TBD

 

  • Kevin Davies

“Editing Mankind,”

Forthcoming 2020, Pegasus

 

  • Michael Specter, Stanford University

Title TBD

Forthcoming 202?, Crown Publishing Group

 

Altered Inheritance – CRISPR and the Ethics of Human Genome Editing

Harvard University Press

HARDCOVER

$24.95 • £19.95 • €22.50

ISBN 9780674976719

Publication Date: 09/17/2019

 

I wish to bring to your attention the following book on Genomics that has in its Part 2 over 100 articles on CRISPR.

  • This book is part of a Series of 16 Books in Medicine

https://lnkd.in/ekWGNqA

available on amazon.com

Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology

Forthcoming 12/2019, Volume Two

by

Prof. Marcus W. Feldman, PhD, Editor, Stanford University

Prof. Stephen J. Williams, PhD, Editor, Temple University

and Aviva Lev-Ari, PhD, RN, Editor, LPBI Group 

 

Part 2: CRISPR for Gene Editing and DNA Repair

2.1 The Science – 77 articles

2.2 Technologies and Methodologies – 27 articles

2.3 Clinical Aspects – 9 articles

2.4 Business and Legal – 18 articles

 

It will be appreciated if you will write a follow up to your 7/2/2019 article to cover this volume (Eight Parts) and all our 16 volumes, BioMed e-Series, 96,000 Page Downloads !!

 

 

SOURCE for Damian Grade’s article in StatNews:

Walter Isaacson is writing a book about CRISPR. He’s got company

By DAMIAN GARDE @damiangarde 7/2/2019

National Biotech Reporter

Damian covers biotech and writes The Readout newsletter.

damian.garde@statnews.com

https://www.statnews.com/2019/07/02/walter-isaacson-crispr-books/?utm_source=STAT+Newsletters

 

Looking forward to hearing from you

Sincerely, yours,

 

Aviva Lev-Ari, PhD, RN

Director & Founder

https://lnkd.in/eEyn69r

Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston

Editor-in-Chief

http://pharmaceuticalintelligence.com

e-Mail: avivalev-ari@alum.berkeley.edu

(M) 617-775-0451

https://cal.berkeley.edu/AvivaLev-Ari,PhD,RN

SkypeID: HarpPlayer83          LinkedIn Profile        Twitter Profile

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Optimization of CRISPR Gene Editing with Gold Nanoparticles

Reporter: Irina Robu, PhD

The CRISPR-Cas9 gene editing system has been welcomed as a hopeful solution to a range of genetic diseases, but the expertise has proven hard to deliver into cells. One plan is to open the cell membrane using an electric shock, but that can accidentally kill the cell. Another is to use viruses as couriers. Problem is, viruses can cause off-target side effects.

CRISPR-Cas9 is a unique technology that enables geneticists and medical researchers to edit parts of the genome by removing, adding or altering sections of DNA sequence. It is faster, cheaper and more accurate than previous techniques of editing DNA and can have a wide range of potential applications.

The CRISPR-Cas9 system consists of two key molecules that introduce a change into the DNA. One is an enzyme called Cas9 which acts as a pair of molecular scissors that can cut the two strands of DNA at a specific location in the genome where bits of DNA can be added or removed. The other one, is a piece of RNA which consists of a small piece of pre-designed RNA sequence located within a longer RNA scaffold. The scaffold part binds to the DNA and pre-designed sequence which contains Cas9. The RNA sequence is designed to find and locate specific sequence in the DNA. The Cas9 trails the guide RNA to the same location in the DNA sequence and makes a cut across both strands of DNA. At this point the cell distinguishes that the DNA is damaged and tries to repair it.

Researchers at Fred Hutchinson Cancer Research Center published new findings in Nature Materials suggested an alternative delivery method such as gold nanoparticles. The gold nanoparticles are packed with all the CRISPR components necessary to make clean gene edits. When the gold nanoparticles were tested in lab models of inherited blood disorders and HIV, between 10% and 20% of the targeted cells were effectively edited, with no toxic side effects.

The researchers use gold nanoparticles to deliver CRISPR to blood stem cells. Each gold nanoparticle contains four CRISPR components, including the enzyme needed to make the DNA cuts. But Fred Hutchinson researchers chose Cas12a, which they believed would lead to more efficient edits. Plus, Cas12a only needs one molecular guide, while Cas9 requires two.
In one experiment, they sought to disturb the gene CCR5 to make cells resistant to HIV. In the second, they created a gene mutation that can protect against blood disorders, including sickle cell disease. They observed the cells encapsulated the nanoparticles within six hours and began the gene-editing process within 48 hours. In mice, gene editing peaked eight weeks after injection, and the edited cells were still in circulation 22 weeks after the treatment.
Researchers at Fred Hutchinson are now working on improving the efficiency of the gold-based CRISPR delivery system so that 50% or more of the targeted cells are edited and are also looking for a commercial partner to bring the technology to clinical phase in the next few years.

SOURCE:

https://www.fiercebiotech.com/research/fred-hutch-team-uses-gold-nanoparticles-to-improve-crispr-gene-editing

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Breakthrough in Gene Editing CRISPR–Cas systems: First example of a fully programmable, RNA-guided integrase and lays the foundation for genomic manipulations that obviate the requirements for double-strand breaks and homology-directed repair.

 

Reporter: Aviva Lev-Ari, PhD, RN

 

CRISPR alternatives for editing genes without cutting: CRISPR 12, 12a, 13, 14 – Alternative Techniques to CRISPR/Cas9

 

  • Alternative to CRISPR/Cas9 – CAST (CRISPR-associated transposase) – A New Gene-editing Approach for Insertion of Large DNA Sequences into a Genome developed @BroadInstitute @MIT @Harvard

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2019/06/11/alternative-to-crispr-cas9-cast-crispr-associated-transposase-a-new-gene-editing-approach-for-insertion-of-large-dna-sequences-into-a-genome-developed-broadinstitute-mit-harvard/

 

  • Vertex Pharmaceuticals agreed to pay $420 million to acquire Exonics and to expand its partnership with CRISPR Therapeutics. The deal sets in motion a planto use CRISPR to treat Duchenne muscular dystrophy and myotonic dystrophy type 1.

 

  • In May, a team at the Fred Hutchinson Cancer Research Center described a method developed there to use gold nanoparticles to carry CRISPR components into cells and to use the Cas12a enzyme to make cleaner cuts than Cas9 typically does.

 

  • A UC Berkeley spinoff, GenEdit, is also developing a gold-based CRISPR system.

 

  • Other recently proposed ideas for improving CRISPR include attaching a hairpin-like guide to RNA to improve the accuracy of DNA cuts and adding an on-off switch to Cas9 enzymes to ensure they can’t make edits anywhere other than the targeted sites.

 

  • The next step for Sternberg’s team at Columbia is to test the INTEGRATE technology in mammalian cells. They believe the technique could eventually be applied to a variety of products, such as gene therapies and engineered crops.

 

Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration

Abstract

Conventional CRISPR–Cas systems maintain genomic integrity by leveraging guide RNAs for the nuclease-dependent degradation of mobile genetic elements, including plasmids and viruses. Here we describe a remarkable inversion of this paradigm, in which bacterial Tn7-like transposons have co-opted nuclease-deficient CRISPR–Cas systems to catalyze RNA-guided integration of mobile genetic elements into the genome. Programmable transposition of Vibrio cholerae Tn6677 in E. coli requires CRISPR- and transposon-associated molecular machineries, including a novel co-complex between Cascade and the transposition protein TniQ. Donor DNA integration occurs in one of two possible orientations at a fixed distance downstream of target DNA sequences, and can accommodate variable length genetic payloads. Deep sequencing experiments reveal highly specific, genome-wide DNA integration across dozens of unique target sites. This work provides the first example of a fully programmable, RNA-guided integrase and lays the foundation for genomic manipulations that obviate the requirements for double-strand breaks and homology-directed repair.

 SOURCE

A CRISPR alternative for editing genes without cutting

Scientists at Columbia University’s Vagelos College of Physicians and Surgeons are now proposing an alternative gene-editing system—one that sidesteps the need for DNA cutting altogether.

The researchers are using a “jumping gene,” or transposon, from a bacterium called Vibrio cholerae. The transposon is able to insert itself into different regions of the genome and can be programmed to carry any DNA sequence to any site. Therefore their technology, which they dubbed INTEGRATE, acts less like molecular scissors and more like molecular glue, they explained in the journal Nature.

“Rather than introduce DNA breaks and rely on the cell to repair the break, INTEGRATE directly inserts a user-defined DNA sequence at a precise location in the genome, a capability that molecular biologists have sought for decades,” said senior author Sam Sternberg, Ph.D., assistant professor of biochemistry and molecular biophysics at Columbia, in a statement. Sternberg recently joined Columbia after a stint working in the lab of CRISPR pioneer Jennifer Doudna at the University of California, Berkeley.

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