Feeds:
Posts
Comments

Archive for the ‘CAST – Alternative to CRISPR/Cas9’ Category


Medicine in 2045 – Perspectives by World Thought Leaders in the Life Sciences & Medicine

Reporter: Aviva Lev-Ari, PhD, RN

 

This report is based on an article in Nature Medicine | VOL 25 | December 2019 | 1800–1809 | http://www.nature.com/naturemedicine

Looking forward 25 years: the future of medicine.

Nat Med 25, 1804–1807 (2019) doi:10.1038/s41591-019-0693-y

 

Aviv Regev, PhD

Core member and chair of the faculty, Broad Institute of MIT and Harvard; director, Klarman Cell Observatory, Broad Institute of MIT and Harvard; professor of biology, MIT; investigator, Howard Hughes Medical Institute; founding co-chair, Human Cell Atlas.

  • millions of genome variants, tens of thousands of disease-associated genes, thousands of cell types and an almost unimaginable number of ways they can combine, we had to approximate a best starting point—choose one target, guess the cell, simplify the experiment.
  • In 2020, advances in polygenic risk scores, in understanding the cell and modules of action of genes through genome-wide association studies (GWAS), and in predicting the impact of combinations of interventions.
  • we need algorithms to make better computational predictions of experiments we have never performed in the lab or in clinical trials.
  • Human Cell Atlas and the International Common Disease Alliance—and in new experimental platforms: data platforms and algorithms. But we also need a broader ecosystem of partnerships in medicine that engages interaction between clinical experts and mathematicians, computer scientists and engineers

Feng Zhang, PhD

investigator, Howard Hughes Medical Institute; core member, Broad Institute of MIT and Harvard; James and Patricia Poitras Professor of Neuroscience, McGovern Institute for Brain Research, MIT.

  • fundamental shift in medicine away from treating symptoms of disease and toward treating disease at its genetic roots.
  • Gene therapy with clinical feasibility, improved delivery methods and the development of robust molecular technologies for gene editing in human cells, affordable genome sequencing has accelerated our ability to identify the genetic causes of disease.
  • 1,000 clinical trials testing gene therapies are ongoing, and the pace of clinical development is likely to accelerate.
  • refine molecular technologies for gene editing, to push our understanding of gene function in health and disease forward, and to engage with all members of society

Elizabeth Jaffee, PhD

Dana and Albert “Cubby” Broccoli Professor of Oncology, Johns Hopkins School of Medicine; deputy director, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

  • a single blood test could inform individuals of the diseases they are at risk of (diabetes, cancer, heart disease, etc.) and that safe interventions will be available.
  • developing cancer vaccines. Vaccines targeting the causative agents of cervical and hepatocellular cancers have already proven to be effective. With these technologies and the wealth of data that will become available as precision medicine becomes more routine, new discoveries identifying the earliest genetic and inflammatory changes occurring within a cell as it transitions into a pre-cancer can be expected. With these discoveries, the opportunities to develop vaccine approaches preventing cancers development will grow.

Jeremy Farrar, OBE FRCP FRS FMedSci

Director, Wellcome Trust.

  • shape how the culture of research will develop over the next 25 years, a culture that cares more about what is achieved than how it is achieved.
  • building a creative, inclusive and open research culture will unleash greater discoveries with greater impact.

John Nkengasong, PhD

Director, Africa Centres for Disease Control and Prevention.

  • To meet its health challenges by 2050, the continent will have to be innovative in order to leapfrog toward solutions in public health.
  • Precision medicine will need to take center stage in a new public health order— whereby a more precise and targeted approach to screening, diagnosis, treatment and, potentially, cure is based on each patient’s unique genetic and biologic make-up.

Eric Topol, MD

Executive vice-president, Scripps Research Institute; founder and director, Scripps Research Translational Institute.

  • In 2045, a planetary health infrastructure based on deep, longitudinal, multimodal human data, ideally collected from and accessible to as many as possible of the 9+ billion people projected to then inhabit the Earth.
  • enhanced capabilities to perform functions that are not feasible now.
  • AI machines’ ability to ingest and process biomedical text at scale—such as the corpus of the up-to-date medical literature—will be used routinely by physicians and patients.
  • the concept of a learning health system will be redefined by AI.

Linda Partridge, PhD

Professor, Max Planck Institute for Biology of Ageing.

  • Geroprotective drugs, which target the underlying molecular mechanisms of ageing, are coming over the scientific and clinical horizons, and may help to prevent the most intractable age-related disease, dementia.

Trevor Mundel, MD

President of Global Health, Bill & Melinda Gates Foundation.

  • finding new ways to share clinical data that are as open as possible and as closed as necessary.
  • moving beyond drug donations toward a new era of corporate social responsibility that encourages biotechnology and pharmaceutical companies to offer their best minds and their most promising platforms.
  • working with governments and multilateral organizations much earlier in the product life cycle to finance the introduction of new interventions and to ensure the sustainable development of the health systems that will deliver them.
  • deliver on the promise of global health equity.

Josep Tabernero, MD, PhD

Vall d’Hebron Institute of Oncology (VHIO); president, European Society for Medical Oncology (2018–2019).

  • genomic-driven analysis will continue to broaden the impact of personalized medicine in healthcare globally.
  • Precision medicine will continue to deliver its new paradigm in cancer care and reach more patients.
  • Immunotherapy will deliver on its promise to dismantle cancer’s armory across tumor types.
  • AI will help guide the development of individually matched
  • genetic patient screenings
  • the promise of liquid biopsy policing of disease?

Pardis Sabeti, PhD

Professor, Harvard University & Harvard T.H. Chan School of Public Health and Broad Institute of MIT and Harvard; investigator, Howard Hughes Medical Institute.

  • the development and integration of tools into an early-warning system embedded into healthcare systems around the world could revolutionize infectious disease detection and response.
  • But this will only happen with a commitment from the global community.

Els Toreele, PhD

Executive director, Médecins Sans Frontières Access Campaign

  • we need a paradigm shift such that medicines are no longer lucrative market commodities but are global public health goods—available to all those who need them.
  • This will require members of the scientific community to go beyond their role as researchers and actively engage in R&D policy reform mandating health research in the public interest and ensuring that the results of their work benefit many more people.
  • The global research community can lead the way toward public-interest driven health innovation, by undertaking collaborative open science and piloting not-for-profit R&D strategies that positively impact people’s lives globally.

Read Full Post »


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

 

A new gene-editing CAST member

In Science, a team led by Jonathan Strecker, Alim Ladha, and core institute member Feng Zhang reports a new gene-editing approach that can precisely and efficiently insert large DNA sequences into a genome. The system, called CRISPR-associated transposase (CAST), is a completely new platform to integrate genetic sequences into cellular DNA, addressing a long-sought goal for precision gene editing. The team molecularly characterized and harnessed the natural CAST system from cyanobacteria, also unveiling a new way that some CRISPR-associated systems perform in nature: not to protect bacteria from viruses, but to facilitate the spread of transposon DNA. Check out more in coverage from STAT and New Scientist.

SOURCE

https://www.broadinstitute.org/news/research-roundup-june-7-2019

 

RNA-guided DNA insertion with CRISPR-associated transposases

Science  06 Jun 2019:
eaax9181
DOI: 10.1126/science.aax9181

Abstract

CRISPR-Cas nucleases are powerful tools to manipulate nucleic acids; however, targeted insertion of DNA remains a challenge as it requires host cell repair machinery. Here we characterize a CRISPR-associated transposase (CAST) from cyanobacteria Scytonema hofmanni which consists of Tn7-like transposase subunits and the type V-K CRISPR effector (Cas12k). ShCAST catalyzes RNA-guided DNA transposition by unidirectionally inserting segments of DNA 60-66 bp downstream of the protospacer. ShCAST integrates DNA into unique sites in the E. coli genome with frequencies of up to 80% without positive selection. This work expands our understanding of the functional diversity of CRISPR-Cas systems and establishes a paradigm for precision DNA insertion.

 

SOURCE

https://science.sciencemag.org/content/early/2019/06/05/science.aax9181

 

Other related articel published in thies Open Access Online Scientific Journal, include:

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

https://pharmaceuticalintelligence.com/2019/06/13/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/

Read Full Post »