RNA Sequencing, Neighborhood Opportunity, Doris Duke Award, Parkway Run & Walk, Gene Editing

 

Start off your holiday weekend with this week's research news roundup from Children's Hospital of Philadelphia. Learn about a new RNA sequencing technique, how neighborhood opportunity is linked to pediatric care, and who among us received Doris Duke Awards. Read on for news of the Citadel Credit Union's commitment to cancer research and how scientists discovered in a proof-of-concept study that it is possible to deliver gene editing to the brain and central nervous system.

Researchers Develop Inexpensive, Easy-to-Use RNA Sequencing Technique

CHOP researchers developed a technology for targeted sequencing of full-length RNA molecules. The technology, TEQUILA-seq, is cost-effective compared with other available methods for RNA sequencing and can be used for a variety of research and clinical purposes. Details of the method appeared in Nature Communications.

RNA sequencing is used to study how changes in RNA molecules can lead to diseases such as cancer. Current "long read" RNA sequencing platforms evaluate molecules that are more than 10,000 bases in length, but they are only modestly effective. Targeted sequencing, which involves enriching specific nucleic acid sequences before sequencing, is a way to overcome this, but can be expensive and complex to do.

"TEQUILA-seq solves that problem by being both inexpensive and easy to use," said co-senior author Lan Lin, PhD, assistant professor of Pathology and Laboratory Medicine, and a member of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics. "The technology can be adapted by users for different purposes, and researchers can choose which genes they want to sequence and make the reagents for target capture in their own labs. This has the potential to accelerate discovery of new diagnostic and therapeutic solutions for a wide range of diseases."

Learn more in this CHOP press release.

Citadel Credit Union Renews Commitment to Parkway Run & Walk

Citadel Credit Union is renewing its partnership with CHOP by committing to sponsorship of the CHOP Parkway Run & Walk through 2027. Citadel will donate at least $1 million over the next four years to support pediatric cancer research at the CHOP Cancer Center.

The Parkway Run & Walk, the largest annual fundraiser for the Cancer Center, celebrated its 20th anniversary last year. Citadel, which has been involved with the event for the last four years, has raised more than $750,000 for the Cancer Center. In 2023, CHOP and Citadel were recognized with the Philadelphia Business Journal's Faces of Philanthropy award for their community impact in 2022, and their charitable work over multiple years.

"On behalf of the Cancer Center, I would like to thank Citadel Credit Union for its ongoing partnership and sponsorship of our annual Parkway Run & Walk," said Stephen Hunger, MD, chief of the Division of Oncology and director of the Center for Childhood Cancer Research. "Citadel's community involvement and generosity not only helps support breakthrough research and exceptional patient care within our Center, but also gets us one step closer to conquering childhood cancer for children all over the world."

The 2023 CHOP Parkway Walk & Run will be held Sunday, Sept. 24.

Learn more in this Citadel press release.

Neighborhood Opportunity Linked to Pediatric Primary Care Outcomes

Researchers in Clinical Futures, a CHOP Research Institute Center of Emphasis, found that neighborhood opportunity, which comprises socioeconomic factors, access to education and healthy environment, is linked to several pediatric primary care outcomes. JAMA Network Open published the study findings by senior author Alexander Fiks, MD, MSCE, Clinical Futures director and fellow researchers.

The cross-sectional observational study used electronic health record data to evaluate clinical factors including up-to-date preventive care, immunization status, presence of obesity, adolescent depression and suicidality, and maternal depression and suicidality, in relation to Childhood Opportunity Index (COI) quintiles. The researchers found that living in higher COI neighborhoods was associated with being up-to-date on preventive care and immunizations, and lower odds of obesity and adolescent and maternal depression and suicidality.

"Understanding these associations can help health systems identify neighborhoods that need additional support and advocate for and develop partnerships with community groups to promote child well-being," the researchers wrote. "The findings underscore the importance of improving access to preventive care in low COI communities."

Anand Bhagwat, MD, PhD

CHOP Scientists Receive Doris Duke Foundation Awards

Congratulations to two CHOP scientists who are among only 21researchers to receive the 2023 Doris Duke Foundation (DDF) award. The awards include fellowships and multi-year grants to advance clinically significant research by providing mentored research funding and time protection to early-career physician scientists. The DDF has been supporting physician scientists for 25 years to develop groundbreaking ideas.

Kaoru Takasaki, MD

Anand Bhagwat, MD, PhD, a fellow in the Department of Pediatrics, received funding for his project, titled "Understanding the Role of Cytokine Release Syndrome in CAR T-cell therapy for Acute Myeloid Leukemia." Kaoru Takasaki, MD, attending physician in the Division of Hematology, received funding for her project, "Dissecting the Interaction of Trisomy 21, GATA1s and STAG2 Mutations in DS Leukemogenesis."

Proof-of-Concept Study Identifies Way to Deliver Gene Editing Tools to the Brain

Researchers from the CHOP Center for Fetal Research and Penn Engineering identified an ionizable lipid nanoparticle (LNP) that can deliver mRNA base editing tools to the brain and found that it can mitigate diseases of the central nervous system (CNS). The findings appear in ACS Nano.

Identifying ways to deliver gene editing tools to the brain and CNS before birth has been a challenge. After scanning a library of ionizable LNPs — microscopic fat bubbles that have a positive charge at a low pH but a neutron charge at physiological conditions in the body —researchers identified LNPs that were ideal to penetrate the blood-brain barrier in fetal and newborn animal models. They showed that the top-performing LNP was able to change a gene-causing mutation and deliver mRNA base editing tools to the brain.

"This proof-of-concept study supports the safety and efficacy of LNPs for the delivery of mRNA-based therapies to the central nervous system," said co-senior author William Peranteau, MD, attending surgeon in the Division of General, Thoracic and Fetal Surgery, and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery.

Study co-leader Rohan Palanki, is a MD-PhD student in the Peranteau Lab.

Learn more.

ICYMI

Catch up on our headlines from our August 18 In the News:

• FDA Approves First Drug to Treat Rare, Severe Bone Disease
• Study Shows Mitochondrial Dysfunction in Heart, Other Organs Caused by COVID-19 Virus
• CHOP Neurologist Shares Headache Expertise on Doctor Radio

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