The centerpiece of this funding surge is the substantial renewal and expansion of Rice’s Genetic Design and Engineering Center (GDEC). Established initially in 2022 with support from CPRIT, GDEC functions as a pivotal biotech core facility dedicated to the development and provision of intricate DNA tools for cancer and biomedical researchers. The infusion of $2 million will facilitate the addition of an automated mammalian cell hub, vastly enhancing GDEC’s capabilities to generate sophisticated cell models and conduct high-throughput, precise manipulation of mammalian cells. This expansion integrates synthetic biology and genome engineering with robotic automation, streamlining complex processes that previously demanded extensive manual effort.

At the core of GDEC’s mission lies the ability to bridge synthetic biology with genome editing technologies, enabling researchers to design novel genetic circuits and engineer specific genomic alterations with high precision. Leveraging CRISPR-based technologies and next-generation DNA synthesis, the center accelerates exploratory cancer biology studies by creating customized cellular models that mimic tumor biology and treatment responses. The automated mammalian cell hub represents a transformative leap, empowering large-scale production and manipulation of these models under tightly controlled conditions, indispensable for in vitro and preclinical testing.

This technological advancement arrives at a crucial juncture when cancer treatment paradigms are rapidly evolving. The five-year relative survival rate for all cancers in the U.S. has climbed to 70%, a notable increase from the less optimistic rates in the 1970s. Breakthroughs in targeted therapies and immunotherapies have catalyzed this progress, focusing scientific efforts on treatments that exploit the biological intricacies of tumors and the immune microenvironment. Immunotherapy, particularly through engineered T cell variants, is among the most promising strategies intensively explored at Rice, where mechanistic insights are coupled with engineering tactics to refine therapeutic efficacy.

Within this broader landscape, three key projects—spearheaded by eminent Rice faculty—are channeling CPRIT support to tackle critical challenges in cancer treatment through innovative biological insights. Assistant Professor Anna-Karin Gustavsson’s work on live visualization techniques aims to decode dynamic biological responses to radiation therapy, leveraging sophisticated imaging and biosensors to inform and optimize next-generation therapeutic protocols. This approach not only refines radiation precision but also uncovers cellular pathways that confer resistance or sensitivity, illuminating pathways for combinatorial interventions.

Professor Peter Lillehoj, an expert in mechanical engineering, approaches cancer immunotherapy from a bioengineering perspective, focusing on the enhancement of cancer-fighting T cells. His research integrates microscale engineering and immunological profiling, striving to optimize T cell activation, persistence, and tumor infiltration. The engineering of these lymphocytes demands precise control over cellular biomechanics and signaling pathways, a frontier where mechanical forces intersect with immunomodulation. This initiative stands to expand the therapeutic repertoire of cell-based immunotherapies, particularly in aggressive hematological malignancies.

In parallel, Professor Cynthia Reinhart-King investigates how aging influences ovarian cancer progression. This examination of the tumor microenvironment within aged tissues sheds light on the altered biophysical and biochemical cues that potentiate cancer spread in elderly populations. Her research transcends traditional molecular biology by embedding principles of tissue mechanics and cellular microenvironmental changes, unveiling age-dependent vulnerabilities that could be exploited for targeted interventions. This holistic perspective is crucial for developing therapies tailored to the complex realities of cancer in aged patients.

Central to these endeavors is the synergy created between innovative core facilities and expert-led research. Gang Bao, Foyt Family Professor of Bioengineering, along with colleagues Caleb Bashor and Elizabeth Gardner, steward the GDEC’s expansive capabilities to provide essential genetic engineering resources. Their leadership ensures the seamless integration of synthetic biology with high-throughput automation, enabling groundbreaking projects in cancer genetics and immunoengineering to proceed at an unprecedented scale and speed. The facility’s robotic platforms execute intricate genome editing, DNA assembly, and cell culture with precision and reproducibility rarely attainable in traditional laboratory environments.

This orchestration of expertise and technology underscores a broader trend in oncology research: the convergence of engineering, synthetic biology, and immunology to develop precise, patient-tailored therapies. The CPRIT-funded expansion at Rice exemplifies how state-of-the-art infrastructure can catalyze collaborative science, accelerate discovery, and ultimately translate into clinical breakthroughs. By automating labor-intensive processes and fostering interdisciplinary research, the GDEC aims to empower the scientific community to overcome complex biological challenges and pioneer novel cancer treatments.

Moreover, the robust institutional support signals a commitment to academic excellence and scientific leadership in Texas, aiming to attract distinguished researchers whose work will enhance cancer research programs significantly. This strategy includes recruiting faculty with diverse expertise capable of bridging fundamental research and translational medicine. The potential expansion of Rice’s research faculty through CPRIT funding is anticipated to spur innovation clusters around cancer biology, cell engineering, and therapeutic development.

The increasing efficacy of cancer treatments owes much to the transition from nonspecific cytotoxic approaches toward therapies designed with molecular and cellular precision. By embracing this evolution, Rice University and CPRIT are affirming their roles as pivotal contributors in the pursuit to understand cancer’s complexity and devise transformative medical interventions. The augmented GDEC facility and supported projects are poised to dissect cancer mechanisms with unprecedented clarity, engineering solutions from cellular constituents upward.

Initiatives like these underscore the essential role of centralized core facilities that couple advanced technology platforms with expert knowledge. Such centers not only democratize access to cutting-edge tools but also enhance reproducibility and throughput in experimental workflows. The GDEC’s continued growth exemplifies this model, which stands as a beacon for collaborative research ecosystems, fostering innovation that can be swiftly translated into clinical contexts.

In essence, the recent CPRIT funding marks a strategic investment in the technological and intellectual infrastructure necessary for next-generation cancer research. Through a coordinated emphasis on genetic engineering, immunotherapy enhancement, and age-related cancer biology, Rice University is positioning itself at the forefront of efforts to transform cancer treatment paradigms. The coming years hold promise for breakthroughs that could redefine patient outcomes and establish new standards in oncological care.

Subject of Research: Cancer research, genetic engineering, immunotherapy, radiation therapy, ovarian cancer, aging and cancer progression

Article Title: Not provided

News Publication Date: June 8, 2026

Web References:
– https://profiles.rice.edu/faculty/anna-karin-gustavsson
– https://profiles.rice.edu/faculty/peter-b-lillehoj
– https://profiles.rice.edu/faculty/cynthia-reinhart-king
– https://profiles.rice.edu/faculty/gang-bao
– https://profiles.rice.edu/faculty/caleb-bashor
– https://profiles.rice.edu/faculty/elizabeth-gardner

Image Credits: Photo by Jeff Fitlow/Rice University

Keywords: Cancer treatments, Cancer immunology, Ovarian cancer, Immunotherapy, Medical treatments, Radiation therapy, Cell therapies, Scientific community, Scientific facilities

This discovery emerges from two complementary studies published simultaneously in the prestigious journal Nature. Together, these studies explore the biological role and the underlying molecular mechanisms of this CRISPR system variant, shedding light on an unanticipated expansion of the CRISPR repertoire in nature. The team’s investigations reveal how this system, identified as a homolog of Cas12f, uses RNA guides not to incise DNA strands, but rather to orchestrate the recruitment of cellular transcriptional machinery, effectively turning genes “on” with surgical precision.

The process pivots on the ability of the CRISPR complex to locate sequences within the genome and attract RNA polymerase, the pivotal enzyme that transcribes DNA into RNA, thereby initiating gene expression. This mode of action marks a stark departure from the gene disruption or knockout methods that dominate current CRISPR applications. By co-opting the cell’s native transcriptional system, this CRISPR variant enables targeted gene activation even in genomic contexts devoid of canonical promoter elements, traditional markers required for gene initiation.

Key to elucidating these molecular intricacies was the use of cryo-electron microscopy (cryo-EM), a state-of-the-art imaging technique that allows visualization of biomolecules at near-atomic resolution under native-like conditions. Led by Leifu Chang, alongside postdoctoral researcher Renjian Xiao and Ph.D. student Dan Xie, the team integrated cryo-EM data with rigorous biochemical assays to decode how the multi-protein CRISPR complex is assembled and harnessed for gene activation. Their findings reveal a precise structural arrangement where the RNA guide aligns the complex on the target DNA, creating a scaffold that recruits RNA polymerase.

The structural revelations are profound: rather than slicing DNA, the CRISPR-Cas12f homologues serve as a programmable beacon that converts a static genetic locus into a dynamic transcriptional hub. This switching mechanism metaphorically transforms CRISPR from its classic role as a mechanical cutter to an intelligent GPS-guided activator that can modulate gene networks with considerable finesse. This nuanced control bypasses many concerns associated with permanent genome modifications, holding particular appeal for therapeutic contexts where temporary or reversible gene activation is desirable.

Importantly, the discovery that gene activation by this system is not contingent upon traditional promoter sequences challenges existing dogma and points to a more diverse landscape of natural gene regulation tools than previously recognized. This finding could reshape how biotechnologists think about gene control, offering unprecedented opportunities to manipulate gene expression in sophisticated and programmable ways. The evolutionary adaptation of CRISPR systems towards transcriptional regulation underscores the versatility and adaptability of microbial defense mechanisms.

Practical implications of this research are far-reaching. Gene activation capabilities could enable more precise disease modeling, where temporal control of pathogenic gene expression is required. Furthermore, new therapeutic strategies might emerge where genes protective against disease or involved in regeneration can be switched on without the risks linked to DNA breakage and mutagenesis. Additionally, as the system is guided by RNA molecules, programming it for diverse gene targets is straightforward, facilitating broad adoption and modular design.

The synergistic studies benefitted notably from Purdue’s advanced Cryo-EM Facility and Proteomics Facility, with funding from the National Institutes of Health (NIH) and the National Science Foundation (NSF), including a CAREER award that supported this endeavor. These resources afforded the precision and depth of analysis necessary to reveal the complex interplay between CRISPR components and host cellular machinery, exemplifying the powerful synergy of cutting-edge imaging and molecular biology.

Leifu Chang highlighted the broader vision driving the work: “Our goal is to understand the fundamental mechanisms of RNA-guided molecular machines. Dissecting how these systems operate at the molecular level sets the foundation for the development of safer, more versatile genome engineering technologies.” The elucidation of non-cleaving, gene-activating CRISPR variants propels this vision forward, promising a suite of tools that leverage nature’s ingenuity to human benefit.

The biological sciences community now faces exciting challenges and opportunities to translate this molecular insight into practical applications. While further refinement and validation in cellular and organismal contexts will be necessary, the potential to harness natural CRISPR diversity opens a new front in genetic engineering—one where control and modulation replace destruction and mutation. This natural evolution of CRISPR highlights the untapped reservoir of molecular functionalities waiting to be discovered in microbial systems.

In sum, these pioneering studies challenge existing paradigms and extend our understanding of CRISPR beyond genome editing as a means of cut-and-paste towards sophisticated gene regulation. This discovery offers not only a blueprint for next-generation genetic tools but also enriches our fundamental appreciation of molecular evolution and genetic circuitry. By turning CRISPR systems into programmable gene activators, scientists have unlocked a powerful strategy to rewrite the genetic playbook with unprecedented precision and safety.

Subject of Research: Natural CRISPR system variant for RNA-guided gene activation without DNA cleavage

Article Title: Exapted CRISPR–Cas12f homologues drive RNA-guided transcription

News Publication Date: 4-Mar-2026

Web References:

• Biological Function Study
• Molecular Mechanism Study

References:

• Chang, L., Xiao, R., Xie, D., et al. (2026). Exapted CRISPR–Cas12f homologues drive RNA-guided transcription. Nature. DOI: 10.1038/s41586-026-10166-7

Image Credits: Purdue University photo by Alisha Willett

Keywords

Genome editing, Gene activation, CRISPR variants, RNA-guided transcription, Cas12f homologues, Cryo-electron microscopy, Transcriptional regulation, Genome engineering, Molecular mechanism, Gene expression, RNA polymerase recruitment, Therapeutic gene control

The University of California, Davis School of Medicine has announced the appointment of Dr. David J. Segal as the new chair of the Department of Biochemistry and Molecular Medicine. A distinguished scientist with over two decades of experience, Segal has established himself as a national leader in the fields of genome engineering and molecular therapeutics. His appointment marks a significant milestone for UC Davis, as the institution looks to advance its research portfolio and clinical applications in genetic and neurological diseases.

Dr. Segal’s research career is marked by groundbreaking contributions to gene-editing technologies, including Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and CRISPR/Cas9-based platforms. These technologies represent a revolutionary toolkit enabling precise and efficient editing of genetic information within living cells, opening unprecedented possibilities for correcting mutations that underlie a myriad of human diseases. His pioneering work has helped to lay the foundation for translating genome editing from a conceptual framework into powerful clinical applications.

Joining the UC Davis faculty in 2005, Segal has been instrumental in redefining what is possible in treating disorders once considered untreatable. His laboratory is particularly focused on neurological and genetic diseases, where his expertise in molecular engineering is creating new therapeutic strategies to target dysfunctional genes. For instance, by developing tools that can reactivate silenced genes or correct gene dosage abnormalities, Dr. Segal’s research addresses fundamental molecular mechanisms that could potentially reverse debilitating disease phenotypes.

Among the rare genetic disorders targeted by Segal’s lab are Angelman syndrome, SYNGAP1 deficiency, ADNP syndrome, neurofibromatosis type 1, and other neurodevelopmental and neurodegenerative conditions. These diseases, while rare individually, collectively affect a larger population than more common conditions such as cancer or AIDS and yet suffer from a critical lack of effective treatments. This stark reality drives Segal’s commitment to not only advancing basic science but also fostering therapeutic innovations that can be broadly accessible to patients in need.

The impact of Segal’s work extends beyond the lab bench into deep collaborations with patient communities. In particular, his interactions with families affected by Angelman syndrome have provided a poignant perspective on the human dimension of rare diseases. This interface between scientific innovation and patient advocacy informs his approach and magnifies the importance of translating molecular research into real-world therapies that reflect patients’ hopes and urgent needs.

Dean Susan Murin of the UC Davis School of Medicine praised Dr. Segal’s appointment, citing his visionary leadership, innovative research program development, and unwavering dedication to mentoring the next generation of scientists. Murin also expressed gratitude for the interim leadership of Dr. Luis Fernando Santana, whose stewardship of the department has been instrumental during the transition period since 2021.

Throughout his career, Segal has authored or co-authored over 120 peer-reviewed publications, and he holds 25 patents, reflecting his substantial contributions to scientific knowledge and technology development. His work has been supported by numerous prestigious grants from the National Institutes of Health (NIH), the California Institute for Regenerative Medicine (CIRM), as well as awards from various foundations and nonprofit organizations focusing on genetic and neurological disorders.

In addition to his roles within the UC Davis School of Medicine, Dr. Segal serves as an investigator with the NIH Somatic Cell Genome Editing Consortium, a major collaborative effort aimed at accelerating somatic genome editing in therapeutic applications. He also holds the position of field chief editor for Frontiers in Genome Editing, a peer-reviewed journal that highlights cutting-edge advancements in the field and fosters discourse around novel gene-editing methodologies.

Dr. Segal’s educational background includes a Bachelor of Science in biology with honors from Cornell University and a Ph.D. in biochemistry from the University of Utah. He conducted postdoctoral research in molecular biology at the Scripps Research Institute in La Jolla, California before embarking on his academic career. Prior to his appointment at UC Davis, he served as an assistant professor in the Department of Pharmacology and Toxicology at the University of Arizona, Tucson.

Within UC Davis, Segal has held several leadership roles that have strengthened interdisciplinary research and graduate education, including co-chairing the Integrative Genetics and Genomics graduate program and serving as associate director of the UC Davis Genome Center. His vision as chair will undoubtedly continue to propel the department to national and international prominence in biomedical research and education.

Segal’s appointment comes at a time when molecular therapeutics and genome editing are rapidly advancing toward clinical reality, promising transformative treatments for diseases previously deemed “incurable.” His work exemplifies the convergence of innovative molecular engineering, patient-centered research, and institutional leadership poised to shape the future of medicine.

With his groundbreaking research and visionary leadership, Dr. David J. Segal is set to lead the UC Davis Department of Biochemistry and Molecular Medicine into a new era of scientific discovery and therapeutic innovation, advancing the frontiers of genome editing to develop novel, accessible treatments for severe genetic and neurological disorders.

Subject of Research: Genome Engineering, Molecular Therapeutics, Rare Genetic and Neurological Disorders
Article Title: David J. Segal Takes Helm at UC Davis Biochemistry and Molecular Medicine Department, Driving Next-Generation Genome Editing Therapies
News Publication Date: Not specified
Web References:
– UC Davis School of Medicine: https://health.ucdavis.edu/medical-school/
– Department of Biochemistry and Molecular Medicine: https://health.ucdavis.edu/biochem/
– Genome Editing Technologies: https://pubmed.ncbi.nlm.nih.gov/21828278/ (ZFNs), https://pubmed.ncbi.nlm.nih.gov/23508559/ (TALENs), https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/ (CRISPR/Cas9)
– UC Davis Genome Center: https://genomecenter.ucdavis.edu/
– UC Davis MIND Institute: https://health.ucdavis.edu/mind-institute/
– NIH Somatic Cell Genome Editing Consortium: https://commonfund.nih.gov/editing
– Frontiers in Genome Editing: https://www.frontiersin.org/journals/genome-editing
– Angelman Syndrome Information: https://angelman.org/about-angelman-syndrome/
– SYNGAP1 Deficiency: https://www.childneurologyfoundation.org/disorder/syngap1-related-disorder/
– ADNP Syndrome: https://medlineplus.gov/genetics/condition/adnp-syndrome/
– Neurofibromatosis Type 1: https://www.ctf.org/nf1/

References: Not explicitly listed but available via linked scientific publications and Google Scholar: https://scholar.google.com/citations?user=s1cRNHIAAAAJ&hl=en&oi=ao

Image Credits: UC Davis School of Medicine

Keywords: Gene therapy, Gene editing, Genome engineering, Biochemistry, Molecular therapeutics, Rare diseases, Neurological disorders, CRISPR, ZFNs, TALENs, Angelman syndrome, Neurodevelopmental disorders

Retroelements are mobile genetic elements that propagate through a copy-and-paste mechanism involving reverse transcription. Among these, site-specific non-long terminal repeat (non-LTR) retrotransposons have long fascinated scientists due to their ability to integrate preferentially into repetitive genomic regions. Classic examples include their targeting of microsatellites and ribosomal DNA genes, which are known hotspots within eukaryotic genomes. This specificity has intrigued geneticists, but the limitations imposed by their natural targeting preferences have historically curtailed their utility for custom genome engineering applications.

The current study addresses these limitations by discovering multiple new families of site-specific retrotransposons using a sophisticated computational pipeline. This approach enabled the identification and biochemical profiling of R2 retrotransposon variants across diverse species, including the zebra finch (Taeniopygia guttata). Key among these discoveries is R2^Tg, an orthologue demonstrating the remarkable ability to be reprogrammed through engineered payloads. The researchers demonstrated that R2^Tg could execute targeted DNA cleavage, reverse transcription, and scarless insertions, thereby opening the door for precise integration of heterologous sequences at novel genomic loci.

To significantly enhance activity and precision, the team devised an innovative fusion of R2^Tg with CRISPR–Cas9 nickase enzymes. This hybrid molecular tool combines the site-specific cleavage capacity of CRISPR technology with the integration capability of retrotransposons. By directing the complex to new DNA sites via guide RNA programming, this fusion facilitates efficient retrotransposon insertion beyond the retrotransposon’s natural preferences. Such a combination not only amplifies targeting versatility but also enables scarless genome editing, which is critical for therapeutic applications where minimizing genomic disruption is paramount.

Further screening efforts led to the isolation of another potent R2 orthologue, R2^Tocc, distinguished by its natural reprogrammability and reduced insertion activity at its native 28S ribosomal DNA target. Integrating R2^Tocc with a SpCas9^H840A nickase generated the engineered system termed STITCHR: site-specific target-primed insertion through targeted CRISPR homing of retroelements. STITCHR exemplifies a modular platform capable of installing edits on a grand scale, ranging from single nucleotide changes to large insertions exceeding 12 kilobases. Notably, it supports payload delivery using either in vitro transcribed RNA or synthetic RNA templates, broadening its applicability across various experimental contexts.

This breakthrough transcends existing genome editing modalities, offering several key advantages. Unlike many integrative approaches, STITCHR performs scarless insertions, leaving no residual sequence ‘scars’ that can disrupt gene function or regulation. Moreover, its ability to operate effectively in both dividing and non-dividing cells addresses a significant limitation faced by traditional gene editing technologies, many of which rely on cell cycle-dependent mechanisms for DNA repair and integration.

Beyond fundamental research, the implications of this technology for therapeutics are profound. Site-specific and scarless integration is a holy grail for gene therapy, where unpredictable insertional mutagenesis and off-target effects have been long-standing concerns. The programmable nature of STITCHR promises to enable precise gene replacement, correction of pathogenic mutations, and delivery of large therapeutic gene cassettes with unprecedented control and safety.

At the mechanistic level, this work sheds light on the evolutionary plasticity of retrotransposon targeting preferences. The natural specificity for repetitive sequences such as rDNA was historically thought to be a hardwired barrier. However, the study reveals that certain R2 family members retain inherent reprogrammability, suggesting potential natural avenues for retargeting through payload engineering. This insight challenges preconceived notions and opens up novel exploration paths to harness retroelements as versatile genome engineering platforms.

From a technical perspective, the integration of CRISPR nickases with retrotransposon reverse transcriptase activity is an elegant solution to the challenge of modular retargeting. Cas9 nickases generate single-strand breaks, which appear to effectively prime the reverse transcription and insertion machinery of the retrotransposon. This fine-tuning circumvents the deleterious double-strand breaks typically associated with conventional CRISPR-Cas9, thereby reducing cytotoxicity and increasing editing efficiency.

Furthermore, the discovery that large payloads, including gene replacements spanning over 12.7 kilobases, can be integrated scarlessly sets STITCHR apart from other insertion technologies that either struggle with payload size or leave behind disruptive sequence motifs. This feature notably expands the therapeutic landscape, where large gene constructs or complex regulatory elements are often required.

The study’s multidimensional approach—combining computational genomics, molecular engineering, and mammalian cell assays—exemplifies the power of interdisciplinary strategies in biotechnology development. By uncovering and exploiting the natural diversity of retrotransposon orthologues, the researchers have constructed a versatile toolbox ready for fine-tuned genome writing across a wide range of biological systems.

Looking forward, the adaptation of STITCHR for in vivo applications promises exciting opportunities. Tailoring programmable, scarless, and efficient insertion systems for tissues and organs resistant to conventional editing could revolutionize gene therapy for genetic diseases, cancer, and regenerative medicine. Additionally, the potential for deploying this technology in non-dividing cells such as neurons opens new frontiers in neuroscience and cell biology research.

In summary, the development of STITCHR marks a transformative step in genome engineering, marrying the natural precision of retrotransposons with the programmability of CRISPR technology. This innovative platform achieves efficient, scarless, and programmable DNA integration, breaking new ground beyond existing gene editing tools. As the scientific community continues to explore and refine this versatile system, its impact is anticipated to ripple through both fundamental biological research and clinical therapeutics, heralding a new era of genomic medicine.

Subject of Research: Site-specific retrotransposon reprogramming and programmable scarless genome integration using engineered retrotransposon-CRISPR fusion systems.

Article Title: Reprogramming site-specific retrotransposon activity to new DNA sites.

Article References:
Fell, C.W., Villiger, L., Lim, J. et al. Reprogramming site-specific retrotransposon activity to new DNA sites. Nature (2025). https://doi.org/10.1038/s41586-025-08877-4

Image Credits: AI Generated