New platform poised to be next generation of genetic medicines

July 16, 2018, City of Hope
City of Hope's Saswati Chatterjee (left), Ph.D., discovered a gene-editing technology that could efficiently and accurately correct the genetic defects that underlie certain diseases. Credit: City of Hope

A City of Hope scientist has discovered a gene-editing technology that could efficiently and accurately correct the genetic defects that underlie certain diseases, positioning the new tool as the basis for the next generation of genetic therapies.

This editing platform, discovered by City of Hope's Saswati Chatterjee, Ph.D., eventually may be used to cure inherited and acquired diseases.

"Our editing platform provides a new tool for the precise correction of genetic mutations in this rapidly growing field," said Chatterjee, senior author of the new study and a professor in the Department of Surgery at City of Hope. "Think of it as swapping out a mutated gene for a healthy gene to correct genetic mutations."

The proof-of-concept study, published in the journal Proceedings of the National Academy of Sciences on July 16, spotlights a promising new gene-editing platform that may eventually be used to treat diseases such as , hemophilia (a condition that reduces the ability of blood to clot) and other genetic disorders, Chatterjee said.

This genome-editing platform, tested using human blood and tissue as well as in preclinical models, is based on a family of nondisease-causing viruses known as adeno-associated viruses (AAV).

"Although injecting viruses into humans may sound alarming, a large portion of the population already has been exposed to AAV with no harmful consequences in their normal life," Chatterjee said.

Chatterjee's research group isolated a subgroup of AAV known as AAVHSCs, which originate from human . The team discovered that AAVHSCs have the ability to efficiently deliver corrective DNA sequences to the nuclei of targeted cells in the body. Through a process called homologous recombination, these corrective sequences replace disease-causing in the genome. Since the therapeutic correction is at the genome level, it should lead to lifelong correction.

"We found that AAVHSC-based editing vectors can efficiently edit the genome following a single administration," Chatterjee said. "We hope to use these properties to develop widespread and accessible genome editing used to treat genetic diseases around the world."

The editing platform works efficiently in stem cells and mature cells, including adult liver and muscle cells. Successful utilization of AAV has the potential to change the world of gene editing, said Yuman Fong, M.D., co-author of the study and the Sangiacomo Family Chair in Surgical Oncology at City of Hope.

"We at City of Hope are attempting to build the foundation for another landmark treatment, like we did for synthetic human insulin," Fong said. "The potential of altering the course of genetic diseases is immense. Pairing the right AAV with blood stem is going to be an instrumental technique for precision medicine, the next frontier of medical treatment."

Chatterjee and her colleagues still have much work to do to characterize how this platform works and to develop it into therapeutics. They will address these questions in future studies.

This year, Chatterjee received a $2 million grant from the California Institute of Regenerative Medicine to develop a permanent cure for hemophilia A.

City of Hope licensed the pioneering AAV gene editing technology exclusively to Homology Medicines Inc. in May 2016. Chatterjee is the scientific co-founder of Homology Medicines and the chair of the company's scientific advisory board. The genetic medicines company went public in March 2018. Homology Medicines has entered into a research and development collaboration with Novartis.

Explore further: CRISPR genome editing technology can correct alpha-1 antitrypsin deficiency

More information: Laura J. Smith el al., "Stem cell-derived clade F AAV mediates high-efficiency homologous recombination-based genome editing," PNAS (2018).

Related Stories

CRISPR genome editing technology can correct alpha-1 antitrypsin deficiency

July 2, 2018
Groundbreaking research demonstrates proof-of-concept for using CRISPR-Cas9 genome editing technology to correct the gene mutation responsible for alpha-1 antitrypsin (AAT) deficiency, successfully making a targeted gene ...

Genome-editing tool could increase cancer risk

June 11, 2018
Therapeutic use of gene editing with the CRISPR-Cas9 technique may inadvertently increase the risk of cancer, according to a new study from Karolinska Institutet, Sweden, and the University of Helsinki, Finland, published ...

Will AAV vectors have a role in future novel gene therapy approaches?

March 20, 2017
Recombinant adeno-associated virus (rAAV) vectors for delivering therapeutic genes have demonstrated their safety in multiple diseases and clinical settings over the years and are a proven and effective tool that can be used ...

Recommended for you

A single missing gene leads to miscarriage

October 19, 2018
A single gene from the mother plays such a crucial role in the development of the placenta that its dysfunction leads to miscarriages. Researchers from the Medical Faculty of Ruhr-Universität Bochum (RUB) have observed this ...

Making gene therapy delivery safer and more efficient

October 18, 2018
Viral vectors used to deliver gene therapies undergo spontaneous changes during manufacturing which affects their structure and function, found researchers from the Perelman School of Medicine at the University of Pennsylvania ...

Student develops microfluidics device to help scientists identify early genetic markers of cancer

October 16, 2018
As anyone who has played "Where's Waldo" knows, searching for a single item in a landscape filled with a mélange of characters and objects can be a challenge. Chrissy O'Keefe, a Ph.D. student in the Department of Biomedical ...

Researchers use brain cells in a dish to study genetic origins of schizophrenia

October 16, 2018
A study in Biological Psychiatry has established a new analytical method for investigating the complex genetic origins of mental illnesses using brain cells that are grown in a dish from human embryonic stem cells. Researchers ...

Why heart contractions are weaker in those with hypertrophic cardiomyopathy

October 16, 2018
When a young athlete suddenly dies of a heart attack, chances are high that they suffer from familial hypertrophic cardiomyopathy (HCM). Itis the most common genetic heart disease in the US and affects an estimated 1 in 500 ...

Importance of cell cycle and cellular senescence in the placenta discovered

October 15, 2018
Working with researchers from Stanford University and St. Anna Children's Cancer Research, researchers from Jürgen Pollheimer's laboratory at the Medical University of Vienna's Department of Obstetrics and Gynecology have ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Jul 16, 2018
I'm skeptical to say the least

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.