NEW YORK (Reuters Health) – Current technology has allowed the identification of genetic mutations associated with various diseases, but there is a growing separation between diagnoses and treatments, according to a new report.
"The genome edition, and CRISPR technology in particular, increasingly allows precise changes to be made in the cells, with extraordinary potential to transform medical care," said Professor Jennifer A. Doudna of the University of California Berkeley

"In the next decade, CRISPR-based therapies could become the standard of care for common and rare genetic diseases and could also accelerate the pace of immunotherapies to treat cancer," he told Reuters Health by email.
"At least 5,000 genetic disorders come from known mutations of a single gene in the human genome," he added. "Together, these monogenic diseases, such as cystic fibrosis, Huntington's chorea, Duchenne muscular dystrophy and sickle cell anemia, affect at least 250 million people. As the genome issue enters the clinic, care will focus on safety, efficiency and the balance between regulation and application speed. "

In a review in Nature, Doudna analyzes the therapeutic opportunities of genome editing and describes what it will take to apply the therapeutic edition of the genome in the real world.

It focuses on CRISPR technology for therapeutic applications in humans. CRISPR-based tools can perform genome editing, base editing and gene regulation.
For any of these methods to be clinically useful, the enzymes used in CRISPR, the associated guide RNAs and any DNA repair template must reach and enter the cells that need genetic repair. Viral vectors, nanoparticles and electroporation of protein-RNA complexes are currently used to allow functional genome editing complexes to reach cells in the target organs.
The clinical utility of genome editing depends on both precision (the proportion of genetic changes inside and outside the objective) and accuracy (the fraction of editions within the objective that produce the desired genetic result). Other important factors include the immunogenicity of bacterial-derived editing proteins, the potential for pre-existing antibodies against CRISPR components to cause inflammation, and the unknown long-term safety and stability of genome editing results.

The clinical potential of therapeutic genome editing has been evaluated in sickle cell disease and other inherited blood disorders, muscular dystrophy and some other monogenetic disorders, but the extreme price of such therapies could hamper progress.
The germline edition can also introduce genetic changes that are inheritable if the edited cells are used to start a pregnancy. This raises a number of ethical and political issues that have not yet been fully addressed.
Currently, a large number of organizations agree that it is not appropriate to perform the germline genome editing that culminates in human pregnancy, but that the in vitro edition of the germline genome in human embryos and gametes should be allowed with supervision and donor consent to facilitate research on the possible future clinical applications of gene editing.
They also agree that future clinical applications of human germline genome editing should not be carried out without convincing medical justification, an evidence base that supports its clinical use, an ethical justification and a transparent public process that Involve all interested.

How to advance technology while ensuring responsible use is the subject of ongoing international commissions whose objective is to write detailed requirements for any possible future clinical use.

"The CRISPR genomic edition has the potential to address the unmet medical needs of millions of people around the world, but we must ensure that, ultimately, personalized CRISPR-based therapies are safe, effective, reasonably priced and widely accessible "said Doudna.

"It is vital that we continue to finance and support basic science," he said. "CRISPR technology was the result of a fundamental research project and now supports the development of a new generation of advanced therapies that can improve the health and well-being of millions."

Professor Doudna is co-founder of several biotechnology companies and inventor of patents for CRISPR related technologies.

SOURCE: Nature, online February 12, 2020.

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