CRISPR/Cas9 Gene Editing in Hepatocellular Carcinoma: Current
Progress and Future Perspectives
Hanyu Zheng
College of biopharmaceuticals, Nanjing University of Chinese Medicine, Nanjing, China
Keywords: CRISPR/Cas9, Hepatocellular Carcinoma (HCC), Gene Therapy.
Abstract: The use of CRISPR/Cas9 gene-editing technology to treat viral hepatitis and hepatocellular carcinoma (HCC)
is examined in this paper. HCC, a deadly cancer with high incidence, poses significant challenges due to late
diagnosis and aggressive progression. CRISPR/Cas9 offers promising avenues for treatment by targeting
genetic mutations, oncogenes, and viral genomes. The technology's ability to disrupt HBV's cccDNA and
silence HCV RNA highlights its potential in viral hepatitis therapy. In HCC, CRISPR/Cas9 can suppress
tumor growth by correcting mutations in critical genes like TP53 and CTNNB1. Obstacles to clinical
translation, however, include immunological reactions, off-target effects, and delivery efficiency. The
document emphasizes the need for advancements in delivery systems, specificity improvements, and ethical
considerations to unlock CRISPR/Cas9's full potential in precision medicine.
1 INTRODUCTION
Hepatocellular carcinoma (HCC) ranks among the
most prevalent and lethal cancers worldwide,
distinguished by its high incidence rate and
unfavorable patient prognoses. According to the
World Health Organization, liver cancer is the
fourth leading cause of cancer-related mortality
globally, with approximately 841,000 new cases
and 781,000 deaths reported annually. In China,
there are approximately 393,000 new cases and
369,000 deaths each year. Chronic infection with
the hepatitis B virus (HBV) constitutes a major
etiological factor for liver cancer. Additional
significant risk factors encompass infection with
the hepatitis C virus (HCV), cirrhosis, alcohol
consumption, and non-alcoholic fatty liver disease.
Notwithstanding considerable progress in surgical
methodologies and the implementation of diverse
therapeutic modalities—including hepatic
resection, orthotopic liver transplantation,
radiofrequency ablation, systemic chemotherapy,
and molecularly targeted therapies, the overall
prognosis for hepatocellular carcinoma (HCC)
continues to be unfavorable. This unfavorable
outcome is predominantly attributed to the tumor's
intrinsic biological aggressiveness, characterized
by rapid progression, high metastatic potential, and
resistance to conventional treatments. Furthermore,
epidemiological data consistently demonstrates that
a substantial proportion of HCC cases are identified
at an advanced clinical stage, often precluding
curative intervention. Late diagnosis is frequently
compounded by the asymptomatic nature of early-
stage HCC and limitations in current surveillance
protocols, particularly in high-risk populations with
chronic liver disease. Consequently, these factors
synergistically contribute to suboptimal long-term
survival rates, underscoring the urgent need for
refined diagnostic algorithms and innovative
therapeutic paradigms in hepatocellular carcinoma
management.
The advent of gene-editing technologies,
particularly the CRISPR/Cas9 system, has
introduced new avenues for the treatment of
hepatocellular carcinoma (HCC). The
CRISPR/Cas9 system, which is derived from the
adaptive immune system of prokaryotic organisms,
enables precise and targeted editing of specific
DNA sequences within living cells. This
technology holds the potential to correct genetic
mutations, silence oncogenes, activate tumor
suppressor genes, and even disrupt viral genomes,
thus offering a powerful tool for the treatment of
HCC.The CRISPR/Cas9 gene-editing platform
constitutes a revolutionary molecular biology tool
comprising two principal components: the Cas9
Zheng, H.
CRISPR/Cas9 Gene Editing in Hepatocellular Carcinoma: Current Progress and Future Perspectives.
DOI: 10.5220/0014465900004933
Paper published under CC license (CC BY-NC-ND 4.0)
In Proceedings of the 1st International Conference on Biomedical Engineering and Food Science (BEFS 2025), pages 241-247
ISBN: 978-989-758-789-4
Proceedings Copyright © 2026 by SCITEPRESS – Science and Technology Publications, Lda.
241

endonuclease and a synthetic single-guide RNA
(sgRNA). Through complementary base pairing,
the sgRNA directs the Cas9 ribonucleoprotein
complex to a precise genomic locus, where the
endonuclease catalyzes the introduction of site-
specific double-strand breaks (DSBs). These DSBs
subsequently undergo repair via one of two primary
cellular mechanisms: non-homologous end joining
(NHEJ) or homology-directed repair (HDR). The
error-prone nature of NHEJ frequently results in
frameshift mutations through small insertions or
deletions, thereby facilitating gene knockout. In
contrast, HDR enables precise sequence
modifications when a homologous donor template
is provided, permitting targeted gene insertion or
specific base-pair alterations. This dual-repair
pathway paradigm underpins the remarkable
versatility of CRISPR/Cas9 in facilitating diverse
genetic modifications, ranging from loss-of-
function mutations to precise gene activation or
regulatory element introduction, thereby serving as
a cornerstone technology in modern molecular
biology and therapeutic development.
Recent research has shown promising potential
for the CRISPR/Cas9 gene-editing system in
treating hepatocellular carcinoma (HCC). For
instance, scientists have used this system to target
and disrupt the covalently closed circular DNA
(cccDNA) of the hepatitis B virus (HBV). This
cccDNA is essential for the virus to stay in the host
and has a major impact on the development of
hepatocellular carcinoma. The CRISPR/Cas9
system can specifically cut cccDNA, which helps to
inhibit viral gene expression and reduce the amount
of viruses in infected cells. Also, CRISPR/Cas9 has
been used to target oncogenes and tumor suppressor
genes in HCC cells, like TP53, CTNNB1, and
MYC, which are often changed in liver cancer. By
fixing these changes or turning off the overactive
oncogenes, CRISPR/Cas9 can slow tumor growth
and make existing treatments work better.
Furthermore, CRISPR/Cas9 has demonstrated
potential in overcoming drug resistance in
hepatocellular carcinoma (HCC). For example,
studies have identified genes such as PHGDH and
HK1, which contribute to resistance to sorafenib
and regorafenib, respectively. By knocking out
these genes using CRISPR/Cas9, researchers have
increased the sensitivity of HCC cells to these
drugs, thereby improving therapeutic outcomes.
Also, CRISPR/Cas9 has been used to target long
noncoding RNAs (lncRNAs) that are important for
HCC progression and metastasis. For example,
removing lncRNAs like SNHG9 and RP11-156P1.3
has been proven to restrain the proliferation,
migration, and invasion of HCC cells. Although
CRISPR/Cas9 has shown great results for HCC
treatment, its clinical use is challenged by delivery
efficiency, off - target effects, and immune
responses. Creating effective and safe delivery
systems (such as viral vectors and nanoparticles) is
key to translating CRISPR/Cas9 technology into
clinical practice. Meanwhile, enhancing the
specificity and minimizing off—target effects of
CRISPR/Cas9 are vital for guaranteeing the safety
and effectiveness of this gene—editing technology.
2 THE DEVELOPMENT AND
APPLICATION OF CRISPR-
CAS9 TECHNOLOGY
CRISPR-Cas9 technology, discovered in 2012 by
Jinek et al. in the paper “A programmable dual-RNA–
guided DNA endonuclease in adaptive bacterial
immunity” published in Science, has rapidly become
a core tool in gene editing (Jinek et al. 2012). Rooted
in the adaptive immune system of bacteria, it
harnesses guide RNA (gRNA) to target specific DNA
sequences with remarkable precision for gene editing.
This technology has not only demonstrated its
prowess in basic research but also holds great promise
in clinical applications. In basic research, CRISPR-
Cas9 allows scientists to delve into the functions of
genes by selectively modifying or deleting them. For
instance, as described in various research studies
similar to the concept presented in an overview of the
evolution of CRISPR/Cas9 and its potential in HCC
therapy, in model organisms like drosophila and
mice, the researchers can use this technology to create
gene knock-out or knock-in, observing the resulting
phenotypic changes to understand the roles of specific
genes in development, metabolism, and disease
mechanisms (Wei et al. 2019). This has significantly
advanced our understanding of biological processes
at the genetic level. Clinically, the potential of
CRISPR-Cas9 is vast. In cancer treatment, it can be
used to target and disrupt oncogenes or repair mutated
tumor - suppressor genes in cancer cells. For
example, in melanoma, although a specific melanoma
- related paper is not cited here, many studies in the
field of cancer treatment, such as a summary of
written works on utilizing CRISPR/Cas9 gene
therapy for hepatocellular carcinoma treatment,
explore the use of CRISPR-Cas9 to target key genes
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in cancer cells (Wu et al. 2020). Knocking out genes
associated with drug resistance can enhance the
sensitivity of tumor cells to chemotherapy. In the
context of genetic diseases, such as sickle cell
anemia, while no specific paper is directly referenced,
numerous research efforts in the area of gene - editing
for genetic diseases aim to correct the mutated gene
responsible for the disease using CRISPR-Cas9
technology, offering hope for patients who previously
had limited treatment options.
However, CRISPR-Cas9 technology's use faces
many difficulties. Off - target effects are a major
concern, as they can cause unintended mutations in
non - target genes. These off - target mutations may
lead to unforeseen consequences, including the
activation of oncogenes or disruption of normal
cellular functions. Immune responses are another
obstacle. The human body may recognize the
introduced Cas9 protein or delivery vectors as
foreign, triggering an immune reaction that can
neutralize the treatment and even cause adverse
effects. These challenges are discussed in
documents like Cutting-edge nano-theranostics of
CRISPR-Cas for viral hepatitis and hepatocellular
carcinoma and “Description of CRISPR/Cas9
development and its prospect in hepatocellular
carcinoma treatment” (Wei et al. 2019, Amjad et al.
2024). To address these issues, researchers are
actively developing more precise gRNA design
methods. By optimizing the gRNA sequence,
scientists aim to improve its binding specificity to
the target DNA, reducing the likelihood of off -
target effects. Additionally, the development of
Cas9 protein variants with lower immunogenicity is
underway. These engineered Cas9 proteins are
designed to evade the immune system's detection,
enabling more effective in vivo applications. In
tandem with these efforts, delivery systems that
combine nanotechnology are being refined. Lipid -
nanoparticle - based delivery systems, for example,
are being optimized to enhance the stability and
targeting of CRISPR-Cas9 components in the body,
ensuring that the technology reaches its intended
target cells while minimizing side effects. As
described in cutting-edge nano-theranostics of
CRISPR-Cas for viral hepatitis and hepatocellular
carcinoma, these progress are essential for
CRISPR-Cas9 technology to be applied
successfully (Amjad et al. 2024).
3 THE USE OF CRISPR-CAS9 IN
MANAGING VIRAL
HEPATITIS
Viral hepatitis, especially that caused by HBV and
HCV, poses a serious threat to global public health as
it can result in severe liver diseases and cancer. The
CRISPR-Cas9 gene - editing system presents new
treatment options for viral hepatitis. For HBV,
cccDNA is the key therapeutic target. It has four long
open reading frames that code for proteins crucial for
the virus to copy itself. Once HBV infects liver cells,
its double-stranded DNA moves into the nucleus to
form cccDNA, which is essential for making new
viruses and maintaining long - term infection. As
mentioned in the review "Advanced
Nanotheranostics of CRISPR Cas for Viral Hepatitis
and Hepatocellular Carcinoma", multiple
CRISPR/Cas9 systems have been created to target the
stable parts of cccDNA in lab and animal studies. For
example, in some studies, CRISPR/Cas9 - mediated
editing achieved a significant decrease in cccDNA
levels in HBV - infected cells, inhibiting viral
replication and potentially reducing the risk of
tumorigenesis associated with HBV infection (Bai et
al. 2020). For HCV, which copies itself in the cell
fluid, the main method is to target its RNA. When
HCV RNA gets into liver cells, it keeps making the
virus. Studies, like those using the FnCas9 system,
have shown that CRISPR/Cas9 can block HCV RNA.
In one experiment, the FnCas9 system with special
RNA - targeting guides was able to lower HCV
protein levels by more than 50%, showing that
CRISPR—Cas9 could be a promising way to treat
HCV—related viral hepatitis (Bai et al. 2020).
However, treating viral hepatitis involves not
only clearing the virus but also repairing liver
damage and modulating immune responses. The
immune system's response to the virus and the
CRISPR - Cas9 system itself is a crucial factor. The
introduced CRISPR/Cas9 components may trigger
immune reactions, which could potentially lead to
cell death or other negative consequences. As
mentioned in "Advanced Nanotheranostics of
CRISPR Cas for Viral Hepatitis and Hepatocellular
Carcinoma", pre - existing immunity to Cas9
proteins, such as SaCas9 and SpCas9, has been
detected in a significant portion of the population,
which may impact the effectiveness of CRISPR -
based therapies (Jinek et al. 2012). Therefore, the
application of CRISPR - Cas9 in viral hepatitis
treatment must be integrated with other therapeutic
CRISPR/Cas9 Gene Editing in Hepatocellular Carcinoma: Current Progress and Future Perspectives
243

approaches, such as antiviral medications and
immune modulators. Conventional antiviral agents
like reverse transcriptase inhibitors and RNA
interference technology have been used to combat
viruses in the liver. Combining these with CRISPR
- Cas9 could enhance the overall therapeutic effect.
For instance, some research has looked into using
mixed treatment methods to focus on various parts
of the virus's life cycle and the host's immune
reaction (Wu et al. 2020).
Additionally, achieving efficient delivery and
specific targeting of CRISPR - Cas9 to the liver
remains a key focus of current research. Delivery
vectors need to overcome several barriers,
including the large size of CRISPR/Cas9 cargos,
degradation by nucleases in physiological fluids,
crossing cell membranes, and potential degradation
in endosomes and lysosomes. Viral vectors,
including adenovirus and adeno-associated virus
(AAV), have served as delivery tools for
CRISPR/Cas9 systems to the liver. But they have
flaws, such as limited packaging ability, possible
integration into the host genome, and immune
response - triggering potential. Liposome - or lipid
- based nanoparticles, polymer - based
nanoparticles, inorganic nanoparticles, cell -
derived nanoparticles, and peptide/protein - based
nanoparticles are being developed as non - viral
vectors. These non - viral vectors have advantages
such as lower immunogenicity and flexible
universality, but they also face challenges like
lower delivery efficiency. Researchers are
exploring ways to optimize these delivery systems,
for example, by modifying the physicochemical
properties of nanoparticles, adding targeting
ligands, and improving endosomal escape
mechanisms (Bai et al. 2020, Amjad et al. 2024).
4 THE APPLICATION OF
CRISPR-CAS9 IN THE
TREATMENT OF
HEPATOCELLULAR
CARCINOMA
Hepatocellular carcinoma (HCC) is one of the most
common cancers globally and a major public health
concern due to its high incidence and death
rates.CRISPR-Cas9 technology has emerged as a
transformative tool in HCC treatment by enabling
precise targeting of oncogenes, tumor suppressors,
and critical signaling pathways. For instance,
CRISPR-mediated knockout of PHGDH
(phosphoglycerate dehydrogenase) disrupts serine
biosynthesis, leading to oxidative stress and enhanced
sensitivity to sorafenib in HCC cells. This approach
has demonstrated efficacy in inhibiting tumor growth
both in vitro and in murine xenograft models (Amjad
et al. 2024). Similarly, targeting CTNNB1 (β-catenin)
using CRISPR-Cas9 disrupts the aberrant Wnt/β-
catenin signaling pathway, effectively reducing cell
proliferation and tumorigenesis in preclinical models.
Restoring TP53 function via CRISPR editing also
shows promise by reactivating cell cycle control and
apoptosis, thereby HCC progression.
Beyond direct gene editing, CRISPR-Cas9 is
being leveraged to reshape the tumor
microenvironment. For example, editing DUSP4
reactivates the ERK/MAPK pathway, sensitizing
HCC cells to tyrosine kinase inhibitors and
potentially augmenting immunotherapy outcomes.
Genome-wide CRISPR screens have also identified
novel targets such as ADAMTSL3, whose
inactivation suppresses HCC proliferation and
metastasis, highlighting its potential as a
therapeutic candidate. Additionally, CRISPR-based
modulation of long noncoding RNAs (lncRNAs)
like SNHG9 and CASC11 has been shown to
disrupt oncogenic pathways, underscoring the
versatility of this technology in addressing HCC's
complex genetic landscape (Lu et al. 2021).
However, translating these findings into clinical
applications faces significant challenges. The
inherent genomic heterogeneity of HCC
necessitates delivery systems capable of achieving
precise and targeted editing while minimizing off-
target effects. Recent advancements in
nanotechnology, such as charge-reversing lipid
nanoparticles, show promise in enhancing CRISPR-
Cas9 delivery to hepatic tumors. Furthermore,
integrating multi-omics data with CRISPR
screening platforms could enable personalized
treatment strategies by identifying actionable
genetic alterations and predicting therapeutic
responses. Addressing these challenges will be
critical to unlocking the full potential of CRISPR-
Cas9 in overcoming HCC's therapeutic resistance
and improving patient outcomes.
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5 DELIVERY SYSTEMS FOR
CRISPR-CAS9 TECHNOLOGY
The effective application of CRISPR-Cas9
technology relies on robust delivery systems to ensure
its precise localization and release within target cells
or tissues. Current delivery systems are mainly
divided into viral and non-viral vectors. Viral vectors,
including AAVs and lentiviruses, provide high
efficiency and sustained expression but risk
triggering immune responses and integrating into the
host genome. For example, AAV vectors have been
widely used in hepatic targeting due to their natural
tropism for hepatocytes, allowing effective CRISPR-
Cas9 delivery to treat viral hepatitis and HCC (Kong
et al. 2021). However, their limited packaging
capacity (<5 kb) restricts the delivery of large genetic
payloads, and pre-existing immunity to AAV
serotypes in humans may reduce therapeutic efficacy.
Lentiviruses, while capable of integrating transgenes
into the host genome, pose oncogenic risks due to
random integration events, necessitating careful
design to avoid insertional mutagenesis.
Non-viral vectors, including liposomes,
polymer nanoparticles, and inorganic
nanomaterials, are characterized by low
immunogenicity and high customizability, though
their delivery efficiency is comparatively lower.
Lipid-nanoparticle (LNP) systems, for instance,
have been optimized to encapsulate CRISPR-Cas9
components and enhance cellular uptake through
endosomal escape mechanisms (Yang et al. 2020).
These LNPs can be surface-functionalized with
ligands targeting specific cell surface receptors,
such as asialoglycoprotein receptors in hepatocytes,
to improve tissue specificity. Polymeric vectors,
such as polyethyleneimine (PEI), offer tunable
physicochemical properties but often require
further modification to reduce cytotoxicity and
improve transfection efficiency. Emerging
inorganic nanomaterials, including gold
nanoparticles and mesoporous silica, have shown
promise in improving intracellular delivery through
their ability to protect nucleic acids from
degradation and facilitate endosomal escape. To
address the limitations of traditional delivery
systems, researchers are developing innovative
platforms with spatiotemporal control.
Extracellular vesicles (EVs), such as exosomes,
have emerged as natural nanocarriers due to their
low immunogenicity and endogenous targeting
capabilities. EVs derived from mesenchymal stem
cells (MSCs) have been engineered to carry
CRISPR-Cas9 components, demonstrating efficient
delivery to hepatic tissues in preclinical models
(Yang et al. 2020).
6 CLINICAL TRANSLATION
AND ETHICAL ISSUES OF
CRISPR-CAS9 TECHNOLOGY
The clinical translation of CRISPR-Cas9 technology
is a hot topic and major challenge in the field of gene
editing. Despite significant progress in laboratory
research, numerous obstacles remain in clinical
applications. First, making sure CRISPR-Cas9 is safe
and works well in humans is key. It needs careful
testing in clinical trials to check for side effects and
long - term results. In sickle cell disease (SCD)
treatment, CRISPR-Cas9 has potential by turning on
fetal hemoglobin (HbF) production. But studies
found it can cause gene - editing errors and DNA
rearrangements, especially in SCD samples. So, a full
safety check is needed (Li et al. 2022). Secondly,
ethical considerations surrounding CRISPR-Cas9
technology have generated extensive debate. Gene
editing could lead to genetic variations and raise
concerns related to germline editing, which may
affect future generations. The international
community is divided on the appropriate scope of
CRISPR applications, with some advocating for a
regulatory framework that accommodates all types of
human genome editing, including germline editing.
Additionally, developing sound regulatory policies
and ethical guidelines to ensure the rational
application of this technology is another problem that
needs to be addressed. By May 2018, at least 15
clinical trials using CRISPR for various diseases were
underway globally. In China, genes of at least 86
people were altered in such trials. This highlights the
need for strong regulations to oversee CRISPR
applications (Hsu et al. 2014).
Moreover, the clinical application of CRISPR-
Cas9 technology also faces challenges in optimizing
delivery systems for efficient gene editing while
minimizing impact on non-target tissues. Enhancing
editing precision and reducing off-target effects are
critical research focuses. Despite these challenges,
CRISPR-Cas9 shows great potential in treating
various diseases, such as precisely repairing gene
mutations for genetic disorders or modulating gene
expression for complex diseases. With technological
advancements and deeper understanding of gene
editing mechanisms, CRISPR-Cas9 is poised to play
CRISPR/Cas9 Gene Editing in Hepatocellular Carcinoma: Current Progress and Future Perspectives
245

a larger role in clinical medicine, offering new
therapeutic options and hope for patients.
7 CONCLUSION
CRISPR-Cas9 technology, from bacterial immune
systems, has transformed gene editing and shows
promise in treating diseases like viral hepatitis and
HCC by enabling precise DNA changes. However,
the transition from laboratory research to clinical
application is complex and multifaceted, requiring
careful navigation of technical, ethical, and
regulatory challenges. In the realm of viral hepatitis,
CRISPR-Cas9 has demonstrated remarkable
potential. For HBV, targeting the covalently closed
circular DNA (cccDNA) represents a critical
advancement, as this viral component persists in
infected cells and hinders cure. Studies have shown
that CRISPR-Cas9 can effectively reduce cccDNA
levels, inhibit viral replication, and potentially
decrease the risk of HCC development. Similarly, for
HCV, RNA-targeting approaches using CRISPR-
Cas9 have shown the ability to silence viral RNA and
reduce viral protein expression. These applications
highlight the versatility of CRISPR-Cas9 in
combating viral infections that pose significant global
health burdens. The treatment of HCC has also been
transformed by CRISPR-Cas9 applications. By
targeting oncogenes such as PHGDH and CTNNB1,
researchers have successfully suppressed tumor
growth and enhanced the efficacy of existing
therapies. The technology's ability to disrupt drug
resistance mechanisms, such as those involving HK1,
further underscores its therapeutic potential.
Additionally, the modulation of long noncoding
RNAs and tumor microenvironment components
demonstrates the comprehensive approach CRISPR-
Cas9 offers in addressing the complex genetics of
HCC.
Despite these advances, several challenges must
be addressed for successful clinical translation. Off-
target effects remain a primary concern, as
unintended edits can lead to serious consequences,
including carcinogenesis. Immune responses to
CRISPR-Cas9 components, particularly Cas9
proteins, may limit therapeutic efficacy and cause
adverse reactions. The development of more specific
guide RNAs, immune-evasive Cas9 variants, and
advanced delivery systems is crucial to mitigate these
issues. Delivery systems represent another critical
area of research. Viral vectors, while efficient, face
limitations such as immunogenicity and packaging
capacity. Non-viral vectors, like lipid nanoparticles
and polymers, have less immunogenicity but need
optimization to enhance delivery efficiency. The
integration of nanotechnology and spatiotemporal
control mechanisms, such as extracellular vesicles,
holds promise for enhancing targeted delivery and
reducing off-target impacts. Ethical and regulatory
considerations are equally important. The potential
for germline editing and unintended genetic
variations has sparked intense debate, with diverse
opinions on the appropriate scope of CRISPR
applications. The establishment of robust regulatory
frameworks is essential to ensure the safe and ethical
use of this technology, particularly as clinical trials
involving CRISPR-Cas9 continue to expand globally.
CRISPR-Cas9 technology leads in precision
medicine, creating unique chances to treat once - hard
- to - manage diseases. The path forward requires a
balanced approach that fosters innovation while
addressing safety, ethical, and regulatory concerns.
Future research should prioritize the development of
more precise editing tools, efficient delivery methods,
and comprehensive ethical guidelines. By doing so,
the scientific community can harness the full potential
of CRISPR-Cas9 to deliver effective therapies and
improve outcomes for patients with viral hepatitis,
HCC, and other debilitating conditions.
REFERENCES
Amjad, E., Pezzani, R., Sokouti, B. 2024.A review of the
literature on the use of CRISPR/Cas9 gene therapy to
treat hepatocellular carcinoma. Oncology Research
32(3):439-461.
Bai, Q., Shao, J., & Cao, J., et al. 2020. Protein kinase C-α
upregulates sodium channel Nav1.9 in nociceptive
dorsal root ganglion neurons in an inflammatory
arthritis pain model of rat. Journal of Cellular
Biochemistry 21(1):768-778.
Hsu, P. D., Lander, E. S., & Zhang, F. 2014. Development
and applications of CRISPR-Cas9 for genome
engineering. Cell 157(6):1262–1278.
Jinek, M.,Chylinski,K.,& Fonfara,I.,et al. 2012. A
programmable dual-RNA-guided DNA endonuclease
in adaptive bacterial immunity. Science 337(6096):
816-821.
Kong, H., Ju, E., & Yi, K. 2021. Advanced
Nanotheranostics of CRISPR/Cas for Viral Hepatitis
and Hepatocellular Carcinoma. Advanced Science
8(24): e2102051.
Li, C., Zhan, W.,&Yang, Z. 2022. Broad neutralization of
SARS-CoV-2 variants by an inhalable bispecific
single-domain antibody. Cell 185(8):1389–1401.
BEFS 2025 - International Conference on Biomedical Engineering and Food Science
246

Lu, J., Ding, Y., & Zhang, W., et al. 2021. SQSTM1/p62
Knockout by Using the CRISPR/Cas9 System Inhibits
Migration and Invasion of Hepatocellular Carcinoma.
Cells 12(9):1238.
Wei, L., Lee, D., & Law, CT. et al. 2019. Genome-wide
CRISPR/Cas9 library screening identified PHGDH as a
critical driver for Sorafenib resistance in HCC. Nature
Communications 10(1): 4681.
Wu, X., Ma, W., & Mei, C., et al. 2020. Description of
CRISPR/Cas9 development and its prospect in
hepatocellular carcinoma treatment. Journal of
Experimental & Clinical Cancer Research
2020:39(1):97.
Yang, Y. C., Chen, Y. H., & Kao, J. H. 2020. Permanent
Inactivation of HBV Genomes by CRISPR/Cas9-
Mediated Non-cleavage Base Editing. Molecular
Therapy Nucleic Acids 20:480–490.
CRISPR/Cas9 Gene Editing in Hepatocellular Carcinoma: Current Progress and Future Perspectives
247