# Precision targeting of bladder cancer using CRISPR technology

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $182,325

## Abstract

ABSTRACT
Chromosome rearrangements are common in cancers and typically occur early in carcinogenesis.
They drive tumor development by altering the expression or function of oncogenes and tumor
suppressor genes by copy number alterations, formation of oncogenic fusions or by alterations of
DNA elements responsible for regulating cancer genes. Despite being a well-known feature of
cancer, discovered over hundred years ago, this common cancer hallmark has not yet been
therapeutically exploited. Now, for the first time, technological advancements in whole genome
sequencing and the development of CRISPR technologies for precision targeting makes it
possible to identify and target chromosome rearrangement junctions (CRJs) in tumor cells. In
addition, recent breakthroughs in in vivo delivery of CRIPR reagents involving nanoparticles will
open new avenues into clinical utilization. In this R21 application, we present a precision CRISPR
approach that aims at targeting cancer-specific CRJs as an untapped Achilles heel common to
all tumors. This CRISPR-based precision approach consists of pairs of CRJ-targeting guide RNAs
(gRNAs) that bring together two parts of a dCas9-conjugated endonuclease, Fok1, leading to its
activation and the induction of lethal DNA double strand breaks (DSBs) specifically in cancer cells.
Regardless of the tumor-driving mechanism, the presence of CRJs will be exploited to selectively
force these cancer cells to die. We have obtained proof-of-principle of the successful targeting of
CRJs with this approach in both colon and bladder cancer cell lines. We have assembled a multi-
disciplinary team with expertise in CRISPR technology and design, lipid nanoparticle delivery
systems and bladder cancer mouse models. With this team in place and with strong evidence of
efficient targeting of CRJs with Fok1-dCas9 in cancer cell lines, we are now primed to develop
and test our approach in pre-clinical cancer models using recently developed breakthrough lipid
nanoparticle delivery technologies. If successfully implemented, this paradigm-shifting precision-
targeting cancer therapeutic platform could be transformative in designing uniform treatments for
all cancer types irrespective of the biology of the tumor.

## Key facts

- **NIH application ID:** 10289763
- **Project number:** 1R21CA263289-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Mats Ljungman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $182,325
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10289763

## Citation

> US National Institutes of Health, RePORTER application 10289763, Precision targeting of bladder cancer using CRISPR technology (1R21CA263289-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10289763. Licensed CC0.

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