This aggressive metastatic cancer has limited treatment options confined to
and radiation. There is a need to
evolve new therapeutic options to tackle TNBC.
A group of researchers led by Peng Guo, PhD and Marsha Moses, PhD, at the
Vascular Biology Program at Boston Children's have successfully used targeted,
in vivo CRISPR
therapy to stall the progress of triple-negative breast cancer.
Gene Editing Stop Breast Cancer Progression?CRISPR gene
editing holds out immense promise in tackling this type of aggressive
However, the challenge was in the delivery of
safe, non-toxic, effective non-viral vector systems for in vivo gene editing.
reports the synthesis and application of a tumor-targeted nanolipogel system
for CRISPR gene editing in TNBC. This approach uses a soft
nanolipogel made of non-toxic hydrogels and fatty molecules.
are then attached to the gel's surface and guide the CRISPR nanoparticles to
the exact tumor site. The antibodies are designed to recognize their target,
ICAM-1 which is a molecule identified by Marsha Moses Lab (one of the study
authors) in 2014 as a novel drug target for TNBC.
The soft and
flexible gel particles successfully fused with the tumor cell membrane and
entered the tumor to deliver the CRISPR load. As the CRISPR system entered the
tumor cells, it knocked out the breast cancer
oncogene Lipocalin 2 (Lcn2) which is
primarily responsible for aggressive tumor growth and metastasis. Knocking
out this oncogene Lcn2 stalled the tumor's aggressive growth and prevented
The treated mice did not show any signs of toxicity.
Gene Editing Safe?
Peng Guo, the
study's first author, used a soft nanoparticle enabled deeper penetration of
the tumor cells with minimal side effects. They can also deliver a larger
CRISPR load using this method. This method safely arrested the tumor growth
by nearly 77 percent with no observed toxicity in normal tissues.
Moses' team, while the study focused on TNBC; they believe this safe CRISPR
platform can be used to treat pediatric cancers and also deliver
conventional drugs to tumor sites.
This system can carry larger load of
drugs and target the tumor precisely and effectively.
The study was
funded by the National Institutes of Health (R01CA185530, 1DP2CA174495) and the
Breast Cancer Research Foundation.
proof-of-principle strategy was used in both mice and human tumor cells and is
patent protected. The study was reported in the journal PNAS
- Novel CRISPR system could halt growth of triple-negative breast cancer - (http://discoveries.childrenshospital.org/triple-negative-breast-cancer-crispr/)
- Therapeutic genome editing of triple-negative breast tumors using a noncationic and deformable nanolipogel - (https://www.pnas.org/content/early/2019/08/20/1904697116)