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. 2023 Oct 9;22:169. doi: 10.1186/s12943-023-01865-0

Table 11.

Nanocarrier-mediated gene therapy for cancer

Gene Therapy Approach Target Gene Delivery Method Transfection Efficiency Gene Expression Level Therapeutic Outcome Description Novelty Advantages Disadvantages References
Viral vectors p53 Adenovirus High High Induces apoptosis Adenovirus is a commonly used vector for gene therapy due to its high transfection efficiency and ability to infect a wide range of cells The use of adenovirus for p53 gene therapy is a novel approach that has shown promising results in preclinical studies High transfection efficiency results in high gene expression levels and improved therapeutic outcomes Adenovirus can induce an immune response, limiting its effectiveness and potential toxicity [49, 50]
Non-viral vectors siRNA Lipid nanoparticles Moderate Moderate Downregulates target gene expression Lipid nanoparticles are a promising non-viral vector for gene therapy due to their biocompatibility and ability to encapsulate and protect nucleic acids The use of lipid nanoparticles for siRNA delivery is a relatively new approach that has shown improved transfection efficiency and gene silencing compared to other non-viral vectors Lower risk of immune response and toxicity compared to viral vectors Lower transfection efficiency and gene expression levels compared to viral vectors [49, 50]
CRISPR-Cas9 PD-1 Gold nanoparticles High High Enhances T cell activity Gold nanoparticles have unique optical and electronic properties that make them promising candidates for gene therapy The use of gold nanoparticles for CRISPR-Cas9 delivery is a cutting-edge approach that has shown promising results in preclinical studies High transfection efficiency and gene expression levels Limited data on long-term safety and potential toxicity [117]
Electroporation IL-12 Electric pulses Moderate High Induces immune response Electroporation is a non-viral method for delivering nucleic acids into cells using brief electric pulses The use of electroporation for IL-12 gene therapy is a novel approach that has shown promising results in preclinical studies Non-toxic and non-immunogenic Requires specialized equipment and expertise [251]
CRISPR-Cas13a KRAS Liposomes High Moderate Downregulates target gene expression CRISPR-Cas13a is a recently discovered RNA-guided ribonuclease system that can be used for RNA editing The use of CRISPR-Cas13a for KRAS gene therapy is a cutting-edge approach that has shown promising results in preclinical studies Specific and efficient targeting of RNA Limited data on long-term safety and potential off-target effects [252]
AAV vectors BDNF Adeno-associated virus High High Enhances neuronal growth and survival Adeno-associated virus (AAV) vectors are a type of viral vector that can be used for gene therapy due to their safety and ability to integrate into the host genome The use of AAV vectors for brain-derived neurotrophic factor (BDNF) gene therapy is a promising approach for treating neurodegenerative diseases Long-term expression and stability Limited packaging capacity and potential immune response [253]
Hybrid viral vectors HER2 Hybrid viral vectors High High Induces apoptosis Hybrid viral vectors combine the advantages of different viral vectors to achieve improved transduction efficiency and specificity The use of hybrid viral vectors for HER2 gene therapy is a promising approach for treating HER2-positive breast cancer Improved transduction efficiency and specificity compared to single viral vectors Potential immune response and toxicity [254]
CRISPR-Cas9 LDLR Gold nanorods Moderate Moderate Upregulates target gene expression Gold nanorods are a type of gold nanoparticle that can be used for gene therapy due to their plasmonic properties The use of gold nanorods for CRISPR-Cas9-mediated LDLR gene therapy is a novel approach that has shown promising results in preclinical studies Non-toxic and biocompatible Limited data on long-term safety and efficacy [117]
Non-viral vectors BRCA1 Polymeric nanoparticles High High Induces DNA repair Polymeric nanoparticles are a type of non-viral vector that can be used for gene therapy due to their versatility and biocompatibility The use of polymeric nanoparticles for BRCA1 gene therapy is a promising approach for treating breast cancer High transfection efficiency and biocompatibility Limited packaging capacity and potential toxicity [49, 50]
In vivo electroporation IL-10 In vivo electroporation High High Suppresses inflammation In vivo electroporation is a non-viral method for delivering nucleic acids into cells in vivo using electric pulses The use of in vivo electroporation for IL-10 gene therapy is a promising approach for treating inflammatory diseases Non-toxic and non-immunogenic Limited data on long-term safety and potential toxicity [255]
CRISPR-Cas12a EGFR Lipid nanoparticles High Moderate Downregulates target gene expression CRISPR-Cas12a is a recently discovered RNA-guided endonuclease system that can be used for gene editing The use of CRISPR-Cas12a for EGFR gene therapy is a novel approach that has shown promising results in preclinical studies Specific and efficient targeting of DNA Limited data on long-term safety and potential off-target effects [256]
mRNA-based vaccines SARS-CoV-2 spike protein Lipid nanoparticles High High Induces immune response mRNA-based vaccines are a novel approach to gene therapy that use messenger RNA (mRNA) to encode a protein of interest and induce an immune response The use of mRNA-based vaccines for the SARS-CoV-2 spike protein is a cutting-edge approach for preventing COVID-19 Rapid and scalable production Potential immune response and toxicity [257]
CRISPR-Cas9 HPRT Zinc-finger nucleases Moderate Moderate Gene correction Zinc-finger nucleases (ZFNs) are a type of engineered DNA-cutting enzyme that can be used for gene editing The use of ZFNs for HPRT gene therapy is a promising approach for treating genetic disorders Specific and efficient targeting of DNA Limited data on long-term safety and potential off-target effects [117, 258]
Viral vectors CFTR Lentivirus High High Induces gene expression Lentivirus is a type of retrovirus that can be used as a vector for gene therapy The use of lentivirus for CFTR gene therapy is a promising approach for treating cystic fibrosis High transduction efficiency and stable gene expression Potential immune response and toxicity [259]
Non-viral vectors VEGF Dendrimers Moderate Moderate Enhances angiogenesis Dendrimers are a type of branched polymer that can be used as a non-viral vector for gene therapy The use of dendrimers for VEGF gene therapy is a novel approach that has shown promising results in preclinical studies Highly customizable and biocompatible Limited transfection efficiency and potential toxicity [260]
CRISPR-Cas9 DMD AAV vectors High High Gene correction Adeno-associated virus (AAV) vectors are a type of viral vector that can be used for gene therapy The use of AAV vectors for DMD gene therapy is a promising approach for treating Duchenne muscular dystrophy Long-term gene expression and safety Limited packaging capacity and potential immune response [117]
mRNA-based therapies OCT4 mRNA electroporation High High Induces cell reprogramming mRNA-based therapies are a novel approach to gene therapy that use messenger RNA (mRNA) to encode a protein of interest The use of mRNA electroporation for OCT4 gene therapy is a cutting-edge approach for inducing cell reprogramming Rapid and customizable production Potential immune response and toxicity [261]
Non-viral vectors MDR1 Nanoparticles Moderate Moderate Downregulates target gene expression Nanoparticles are a type of non-viral vector that can be used for gene therapy due to their size and biocompatibility The use of nanoparticles for MDR1 gene therapy is a promising approach for overcoming multidrug resistance in cancer Non-toxic and biocompatible Limited transfection efficiency and gene expression levels [49, 50]
CRISPR-Cas9 HBB Lipid nanoparticles High High Gene correction Lipid nanoparticles are a type of non-viral vector that can be used for gene therapy due to their biocompatibility and ease of production The use of lipid nanoparticles for HBB gene therapy is a promising approach for treating sickle cell disease Non-immunogenic and scalable production Limited transfection efficiency and gene expression levels [117]
Gene silencing BCL-2 Aptamers High Moderate Downregulates target gene expression Aptamers are a type of synthetic nucleic acid that can be used as a gene silencing agent The use of aptamers for BCL-2 gene therapy is a novel approach that has shown promising results in preclinical studies Specific and efficient targeting of RNA Limited in vivo stability and potential immunogenicity [262]
Non-viral vectors FGF2 Cationic liposomes Moderate Moderate Enhances angiogenesis Cationic liposomes are a type of non-viral vector that can be used for gene therapy due to their ability to interact with cell membranes The use of cationic liposomes for FGF2 gene therapy is a promising approach for promoting tissue regeneration Low toxicity and customizable Limited transfection efficiency and stability [49, 50, 263]
CRISPR-Cas9 CFTR CRISPR-Cas9 ribonucleoprotein High High Gene correction CRISPR-Cas9 ribonucleoprotein is a recently developed gene editing technology that uses RNA-guided endonucleases The use of CRISPR-Cas9 ribonucleoprotein for CFTR gene therapy is a promising approach for treating cystic fibrosis High specificity and efficiency Potential off-target effects and immune response [117, 264]
RNA interference KRAS Gold nanoparticles Moderate Moderate Downregulates target gene expression Gold nanoparticles are a type of nanoparticle that can be used for gene therapy due to their unique optical and electronic properties The use of gold nanoparticles for KRAS gene therapy is a novel approach that has shown promising results in preclinical studies High biocompatibility and stability Limited transfection efficiency and potential toxicity [194, 195]
Viral vectors APOE Adenovirus High High Upregulates target gene expression Adenovirus is a type of viral vector that can be used for gene therapy due to its high transduction efficiency The use of adenovirus for APOE gene therapy is a promising approach for treating Alzheimer's disease High transduction efficiency and long-term gene expression Potential immune response and toxicity [265]
RNA interference TP53 Nanoparticles High High Downregulates target gene expression Nanoparticles are a type of non-viral vector that can be used for gene therapy due to their size and biocompatibility The use of nanoparticles for TP53 gene therapy is a promising approach for treating various cancers Non-toxic and biocompatible Limited transfection efficiency and gene expression levels [193]
Gene editing F9 CRISPR-Cas9 High High Gene correction CRISPR-Cas9 is a gene editing technology that uses RNA-guided endonucleases to modify DNA The use of CRISPR-Cas9 for F9 gene therapy is a promising approach for treating hemophilia B High specificity and efficiency Potential off-target effects and immune response [266]
mRNA-based therapies FLT3L mRNA electroporation High High Induces immune response mRNA-based therapies are a novel approach to gene therapy that use messenger RNA (mRNA) to encode a protein of interest The use of mRNA electroporation for FLT3L gene therapy is a cutting-edge approach for enhancing immune response Rapid and customizable production Potential immune response and toxicity [194, 195]