Gene therapy

Gene therapy is the use of genes or genetic material to treat or prevent disease. Types of gene therapy include replacing a mutated gene with a healthy copy, inactivating or knocking out a mutated gene, orand introducing a new gene to fight disease. Instead of delivering an entire gene, gene editing can deliver genetic material that edits DNA within a cell. In vivo gene therapy approaches directly introduce the gene therapy into the body. Ex vivo approaches in gene therapy first remove cells from the patient, and genetic modification occurs outside the body, followed by the reintroduction of cells back into the patient. RNA-based and RNA-targeted therapeutics, such as siRNA and antisense oligonucleotides, are considered gene therapy.

Luxterna—FDA and Health Canada approved in-vivo AAV (Adeno-associated virus) gene therapy product for Leber congenital amaurosis (LCA).

• Luxterna—FDA and Health Canada approved in-vivo AAV (Adeno-associated virus) gene therapy product for Leber congenital amaurosis (LCA).

Abecma—CAR-T cell therapy for multiple melanomas

ARI-0001—CAR-T therapy approved by the Spanish Agency for Medicines and Health Products (AEMPS) for acute lymphoblastic leukemia

Breyanzi—CAR-T therapy for large B cell lymphoma

Carteyva—CAR-T therapy approved by the China National Medical Products Administration (NMPA) for large B cell lymphoma and follicular lymphoma

Carvykti—CAR-T therapy FDA-approved for multiple myeloma

Kymriah—FDA-approved CAR-T therapy for B cell acute lymphoma and follicular lymphoma

Tecartus - FDA—approved CAR-T therapy for refractory B-cell precursor acute lymphoblastic leukemia

Yescarta—FDA-approved CAR-T therapy for large B-cell lymphoma and follicular lymphoma

• Abecma—CAR-T cell therapy for multiple melanomas
• ARI-0001—CAR-T therapy approved by the Spanish Agency for Medicines and Health Products (AEMPS) for acute lymphoblastic leukemia
• Breyanzi—CAR-T therapy for large B cell lymphoma
• Carteyva—CAR-T therapy approved by the China National Medical Products Administration (NMPA) for large B cell lymphoma and follicular lymphoma
• Carvykti—CAR-T therapy FDA-approved for multiple myeloma
• Kymriah—FDA-approved CAR-T therapy for B cell acute lymphoma and follicular lymphoma
• Tecartus - FDA—approved CAR-T therapy for refractory B-cell precursor acute lymphoblastic leukemia
• Yescarta—FDA-approved CAR-T therapy for large B-cell lymphoma and follicular lymphoma

Oncolytic viruses are genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells and do not harm normal tissues.

Delytact—conditional approval in Japan for oncolytic virus therapy for brain cancer; the product is a triple-mutated, replication-conditional herpes simplex virus type 1 (HSV-1)

Imlygic—FDA-approved engineered human herpes simplex virus (HSV) as an oncolytic virus to treat advanced melanoma

Oncorine—Oncolytic virus approved in China, indicated for nasopharyngeal carcinoma

T‐Vec—Approved in USA and Europe, oncolytic herpes simplex virus type 1 (HSV‐1) with the gene GM‐CSF to treat melanoma

• Oncolytic viruses are genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells and do not harm normal tissues.
• Delytact—Conditional approval in Japan for oncolytic virus therapy for brain cancer; the product is a triple-mutated, replication-conditional herpes simplex virus type 1 (HSV-1)
• Imlygic—FDA-approved engineered human herpes simplex virus (HSV) as an oncolytic virus to treat advanced melanoma
• Oncorine—Oncolytic virus approved in China, indicated for nasopharyngeal carcinoma
• T‐Vec—Approved in USA and Europe, oncolytic herpes simplex virus type 1 (HSV‐1) with the gene GM‐CSF to treat melanoma

Gendicine—approved in China, recombinant human p53 adenovirus for head and neck cancers

• Gendicine—Approved in China, recombinant human p53 adenovirus for head and neck cancers

Amondys 45—Exon skipping therapy for Duchenne muscular dystrophy (DMD)

Viltepso (Nippon Shinyaku)—Approved in Japan and the US, exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)

Vyondys 53 (Serepta Therapeutics)—FDA-approved exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)

• Amondys 45—Exon skipping therapy for Duchenne muscular dystrophy (DMD)
• Viltepso (Nippon Shinyaku)—Approved in Japan and the US, exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)
• Vyondys 53 (Serepta Therapeutics)—FDA-approved exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)

Leqvio—Approved in the UK and US to treat high cholesterol, small interfering RNA (siRNA) given by subcutaneous injection that reduces low-density lipoprotein cholesterol

• Leqvio—Approved in the UK and US to treat high cholesterol, small interfering RNA (siRNA) given by subcutaneous injection that reduces low-density lipoprotein cholesterol

Collategene—approved in Japan, plasmid DNA encoding human hepatocyte growth factor to treat critical limb ischemia

• Collategene—Approved in Japan, plasmid DNA encoding human hepatocyte growth factor to treat critical limb ischemia

Invossa—was approved in Korea and later suspended; for treatment of knee osteoarthritis

• Invossa—Was approved in Korea and later suspended; for treatment of knee osteoarthritis

Neovasculgen—Approved in Russia for peripheral artery disease

• Neovasculgen—Approved in Russia for peripheral artery disease

Givlaari—FDA-approved to treat acute hepatic porphyria (AHP)

Libmeldy—Approved in the UK to treat metachromatic leukodystrophy (MLD)

Onpattro—RNAi therapeutic approved in the United States and Canada for cardiomyopathy and polyneuropathy due to transthyretin-mediated (ATTR) amyloidosis

Oxlumo—FDA-approved RNAi therapeutic for the kidney disease, primary hyperoxaluria type 1 (PH1)

Skysona—FDA-approved, ex vivo transduction of functional ABCD1 genes with the Lenti-D lentiviral into the patient's hematopoietic stem cells for the treatment of cerebral adrenoleukodystrophy (CALD)

Stremvelis—EMA-approved, used ex vivo to treat combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID)

Tegsedi—FDA-approved antisense oligonucleotide inhibitor of the transthyretin (TTR) protein for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis

Waylivra—EMA-approved, antisense oligonucleotide apolipoprotein C-III (ApoC-III) inhibitor used to treat familial chylomicronaemia syndrome (FCS)

Zolgensma—FDA-approved SMN1 DNA delivered via AAV vector gene therapy indicated for pediatric spinal muscular atrophy (SMA)

Zynteglo—FDA- and EMA-approved, autologous hematopoietic stem cells transduced ex vivo with lentiglobin BB305 lentiviral vector encoding the β-globin gene derivative (βAT87Q-globin) for treatment of ß-thalassemia

• Givlaari—FDA-approved to treat acute hepatic porphyria (AHP)
• Libmeldy—Approved in the UK to treat metachromatic leukodystrophy (MLD)
• Onpattro—RNAi therapeutic approved in the United States and Canada for cardiomyopathy and polyneuropathy due to transthyretin-mediated (ATTR) amyloidosis
• Oxlumo—FDA-approved RNAi therapeutic for the kidney disease, primary hyperoxaluria type 1 (PH1)
• Skysona—FDA-approved, ex vivo transduction of functional ABCD1 genes with the Lenti-D lentiviral into the patient's hematopoietic stem cells for the treatment of cerebral adrenoleukodystrophy (CALD)
• Stremvelis—EMA-approved, used ex vivo to treat combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID)
• Tegsedi—FDA-approved antisense oligonucleotide inhibitor of the transthyretin (TTR) protein for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis
• Waylivra—EMA-approved, antisense oligonucleotide apolipoprotein C-III (ApoC-III) inhibitor used to treat familial chylomicronaemia syndrome (FCS)
• Zolgensma—FDA-approved SMN1 DNA delivered via AAV vector gene therapy indicated for pediatric spinal muscular atrophy (SMA)
• Zynteglo—FDA- and EMA-approved, autologous hematopoietic stem cells transduced ex vivo with lentiglobin BB305 lentiviral vector encoding the β-globin gene derivative (βAT87Q-globin) for treatment of ß-thalassemia

Gene therapy is the use of genes or genetic material to treat or prevent disease. Types of gene therapy include replacing a mutated gene with a healthy copy, inactivating or knocking out a mutated gene, or introducing a new gene to fight disease. Instead of delivering an entire gene, gene editing can deliver genetic material that edits DNA within a cell. In vivo gene therapy approaches directly introduce the gene therapy into the body. Ex vivo approaches in gene therapy first remove cells from the patient, and genetic modification occurs outside the body, followed by the reintroduction of cells back into the patient. RNA-based and RNA-targeted therapeutics, such as siRNA and antisense oligonucleotides, are considered gene therapy.

Adeno-associated viruses (AAVs) are the most popular delivery systems for gene therapy in clinical trials as of 2022. Early- and late-stage clinical trials for hemophilia, inherited blindness, and muscular dystrophy have been successful in terms of safety and efficacy. AAVs are non-pathogenic, have low immunogenicity, infect a broad range of cell types, and are able to achieve efficient and long-lived gene transfer.

AAV was originally discovered as a contaminant in simian adenovirus preparation, and was later found to integrate into the host genome during the latent state of the viral life cycle. For productive replication, AVV relies on co-infection with a helper virus, such as adenovirus or herpes-virusherpes virus. For gene transfer applications, the gene of interest is inserted into replication defectivereplication-defective AAV viral-like particles (recombinant AAV or rAAV) in which viral open reading frames have been removed.

One challenge for AAV vector-based gene therapies is pre-existing humoral immunity to AAV capsids, antibodies to AAV present due to exposure to wild-type AAV, which are common in the environment. Patients are often excluded from clinical trials due to pre-existing neutralizing antibodies that might reduce transduction efficiency. Other challenges include poor transduction efficiency in certain tissues, and low organ specificity, and patients show vector dose-dependent toxicity. The high cost of production of rAAV is also an obstacle to its use in gene therapy.

A CRISPR/Cas9-based strategy, termed homology-independent targeted insertion (HITI), enables targeted gene insertion in non-dividing cells, both in vitro and in vivo. This technique was developed to overcome a barrier to gene therapy in that many technologies are not able to target non-dividing cells such as neurons.

The majority of gene therapies in clinical trials between 2010 and 2020 were for the treatment of cancer. Ex-vivo gene therapy is an approach to developing immunotherapy. CAR T-based immunotherapies are generated by engineering T cells to express chimeric receptors on their surface, allowing them to react to specific molecules such as tumor-associated antigens.

Luxterna - FDALuxterna—FDA and Health Canada approved in-vivo AAV (Adeno-associated virus) gene therapy product for Leber congenital amaurosis (LCA).

Abecma - CAR-TAbecma—CAR-T cell therapy for multiple melanomoamelanomas

ARI-0001 - CAR-TARI-0001—CAR-T therapy approved by the Spanish Agency for Medicines and Health Products (AEMPS) for acute lymphoblastic leukaemialeukemia

Breyanzi - CAR-TBreyanzi—CAR-T therapy for large B cell lymphoma

Carteyva - CAR-TCarteyva—CAR-T therapy approved by the China National Medical Products Administration (NMPA) for large B cell lymphoma and follicular lymphoma

Carvykti - CAR-TCarvykti—CAR-T therapy FDA approvedFDA-approved for multiple myeloma

Kymriah - FDA approvedKymriah—FDA-approved CAR-T therapy for B cell acute lymphoma and follicular lymphoma

Tecartus - FDA approvedFDA—approved CAR-T therapy for refractory B-cell precursor acute lymphoblastic leukemia

Yescarta - FDA approvedYescarta—FDA-approved CAR-T therapy for large B-cell lymphoma and follicular lymphoma

Oncolytic viruses are genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells and do not harm normal tissues.

Delytact - conditionalDelytact—conditional approval in Japan for oncolytic virus therapy for brain cancer,; the product is a triple-mutated, replication-conditional herpes simplex virus type 1 (HSV-1)

Imlygic - FDA approvedImlygic—FDA-approved engineered human herpes simplex virus (HSV) as an oncolytic virus to treat advanced melanoma

Oncorine - OncolyticOncorine—Oncolytic virus approved in China, indicated for nasopharyngeal carcinoma

T‐Vec - ApprovedT‐Vec—Approved in USA and Europe, oncolytic herpes simplex virus type 1 (HSV‐1) with the gene GM‐CSF to treat melanoma

Gendicine - approvedGendicine—approved in China, recombinant human p53 adenovirus for head and neck cancers

Amondys 45 - Exon45—Exon skipping therapy for Duchenne muscular dystrophy (DMD)

Viltepso (Nippon Shinyaku) - Approved—Approved in Japan and the US, exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)

Vyondys 53 (Serepta Therapeutics) - FDA approved—FDA-approved exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)

Leqvio - ApprovedLeqvio—Approved in the UK and US to treat high cholesterol, small interfering RNA (siRNA) given by subcutaneous injection that reduces low-density lipoprotein cholesterol

Collategene - approvedCollategene—approved in Japan, plasmid DNA encoding human hepatocyte growth factor to treat critical limb ischemia

Invossa - wasInvossa—was approved in Korea and later suspended,; for treatment of knee osteoarthritis

Neovasculgen - ApprovedNeovasculgen—Approved in Russia for peripheral artery disease

Givlaari - FDA approvedGivlaari—FDA-approved to treat acute hepatic porphyria (AHP)

Libmeldy - ApprovedLibmeldy—Approved in the UK to treat metachromatic leukodystrophy (MLD)

Onpattro - RNAiOnpattro—RNAi therapeutic approved in the United States and Canada for cardiomyopathy and polyneuropathy due to transthyretin-mediated (ATTR) amyloidosis

Oxlumo - FDA approvedOxlumo—FDA-approved RNAi therapeutic for the kidney disease, primary hyperoxaluria type 1 (PH1)

Skysona - FDA approvedSkysona—FDA-approved, ex vivo transduction of functional ABCD1 genes with the Lenti-D lentiviral into the patient's hematopoietic stem cells for the treatment of cerebral adrenoleukodystrophy (CALD)

Stremvelis - EMA approvedStremvelis—EMA-approved, used ex vivo to treat combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID)

Tegsedi - FDA approvedTegsedi—FDA-approved antisense oligonucleotide inhibitor of the transthyretin (TTR) protein for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis

Waylivra - EMA approvedWaylivra—EMA-approved, antisense oligonucleotide apolipoprotein C-III (ApoC-III) inhibitor used to treat familial chylomicronaemia syndrome (FCS)

Zolgensma - FDA approvedZolgensma—FDA-approved SMN1 DNA delivered via AAV vector gene therapy indicated for pediatric spinal muscular atrophy (SMA)

Zynteglo - FDA and EMA approved, autologous hematopoietic stem cells transduced ex vivo with lentiglobin BB305 lentiviral vector encoding the β-globin gene derivative (βAT87Q-globin) for treatment of ß-thalassemia

Zynteglo—FDA- and EMA-approved, autologous hematopoietic stem cells transduced ex vivo with lentiglobin BB305 lentiviral vector encoding the β-globin gene derivative (βAT87Q-globin) for treatment of ß-thalassemia

Gene Therapytherapy is the use of genes or genetic material to treat or prevent disease. Types of gene therapy include replacing a mutated gene with a healthy copy, inactivating or knocking out a mutated gene or introducing a new gene to fight disease. Instead of delivering an entire gene, gene editing can deliver genetic material that edits DNA within a cell. In vivo gene therapy approaches directly introduce the gene therapy into the body. Ex vivo approaches in gene therapy first remove cells from the patient and genetic modification occurs outside the body, followed by reintroduction of cells back into the patient. RNA-based and RNA-targeted therapeutics such as siRNA and antisense oligonucleotides are considered gene therapy.

Luxterna - FDA and Health Canada approved in-vivo AAV (Adeno-associated virus) gene therapy product for Leber congenital amaurosis (LCA)

Tecartus - FDA approved CAR-T therapy for refractory B-cell precursor acute lymphoblastic leukemia

Yescarta - FDA approved CAR-T therapy for large B-cell lymphoma and follicular lymphoma

Oncorine - Oncolytic virus approved in China, indicated for nasopharyngeal carcinoma

Viltepso (Nippon Shinyaku) - Approved in Japan and the US, exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)

Vyondys 53 (Serepta Therapeutics) - FDA approved exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)

Neovasculgen - Approved in Russia for peripheral artery disease

Luxterna - FDA and Health Canada approved in-vivo AAV (Adeno-associated virus) gene therapy product for Leber congenital amaurosis (LCA)

Neovasculgen - Approved in Russia for peripheral artery disease

Oncorine - Oncolytic virus approved in China, indicated for nasopharyngeal carcinoma

Onpattro - RNAi therapeutic approved in the United States and Canada for cardiomyopathy and polyneuropathy ofdue to hATTRtransthyretin-mediated (ATTR) amyloidosis

Oxlumo - FDA approved RNAi therapeutic for the kidney disease, primary hyperoxaluria type 1 (PH1)

Stremvelis - EMA approved, used ex vivoex vivo to treat combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID)

Tecartus - FDA approved CAR-T therapy for refractory B-cell precursor acute lymphoblastic leukemia

Viltepso (Nippon Shinyaku) - Approved in Japan and the US, exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)

Vyondys 53 (Serepta Therapeutics) - FDA approved exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)

Yescarta - FDA approved CAR-T therapy for large B-cell lymphoma and follicular lymphoma

Zynteglo - FDA and EMA approved, autologous hematopoietic stem cells transduced ex vivo with lentiglobin BB305 lentiviral vector encoding the β-globin gene derivative (βAT87Q-globin) for treatment of ß-thalassemia

Most gene therapies use a viral vector to deliver genetic material into cells.

Most gene therapies use a viral vector to deliver genetic material into cells. Adeno-associated viruses (AAVs) are the most popular delivery systems for gene therapy in clinical trials as of 2022. Early- and late-stage clinical trials for hemophilia, inherited blindness and muscular dystrophy have been successful in terms of safety and efficacy. AAVs are non-pathogenic, have low immunogenicity, infect a broad range of cell types and are able to achieve efficient and long-lived gene transfer.

Gene Therapy is the use of genes or genetic material to treat or prevent disease. Types of gene therapy include replacing a mutated gene with a healthy copy, inactivating or knocking out a mutated gene or introducing a new gene to fight disease. Instead of delivering an entire gene, gene editing can deliver genetic material that edits DNA within a cell. In vivo gene therapy approaches directly introduce the gene therapy into the body. Ex vivo approaches in gene therapy first remove cells from the patient and genetic modification occurs outside the body, followed by reintroduction of cells back into the patient. RNA-based and RNA-targeted therapeutics such as siRNA and antisense oligonucleotides are considered gene therapy.

Amondys 45 - Exon skipping therapy for Duchenne muscular dystrophy (DMD)

Carteyva - CAR-T therapy approved by the China National Medical Products Administration (NMPA) for large B cell lymphoma and follicular lymphoma

Collategene - approved in Japan to treat critical limb ischemia

Delytact - conditional approval in Japan for oncolytic virus therapy for brain cancer

Gendicine - approved in China for head and neck cancers

Givlaari - FDA approved to treat acute hepatic porphyria (AHP)

Imlygic - FDA approved engineered human herpes simplex virus (HSV) as an oncolytic virus to treat advanced melanoma

Invossa - was approved in Korea and later suspended, for treatment of knee osteoarthritis

Oncolytic viruses are genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells and do not harm normal tissues.

Delytact - conditional approval in Japan for oncolytic virus therapy for brain cancer, product is a triple-mutated, replication-conditional herpes simplex virus type 1 (HSV-1)

Imlygic - FDA approved engineered human herpes simplex virus (HSV) as an oncolytic virus to treat advanced melanoma

T‐Vec - Approved in USA and Europe, oncolytic herpes simplex virus type 1 (HSV‐1) with the gene GM‐CSF to treat melanoma

Gendicine - approved in China, recombinant human p53 adenovirus for head and neck cancers

Amondys 45 - Exon skipping therapy for Duchenne muscular dystrophy (DMD)

Leqvio - Approved in the UK and US to treat high cholesterol, small interfering RNA (siRNA) given by subcutaneous injection that reduces low-density lipoprotein cholesterol

Collategene - approved in Japan, plasmid DNA encoding human hepatocyte growth factor to treat critical limb ischemia

Invossa - was approved in Korea and later suspended, for treatment of knee osteoarthritis

Givlaari - FDA approved to treat acute hepatic porphyria (AHP)

Viltepso (Nippon Shinyaku) - FDAApproved in Japan and approvedthe US, exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)

Waylivra

Yescarta

Waylivra - EMA approved, antisense oligonucleotide apolipoprotein C-III (ApoC-III) inhibitor used to treat familial chylomicronaemia syndrome (FCS)

Yescarta - FDA approved CAR-T therapy for large B-cell lymphoma and follicular lymphoma

Zolgensma - FDA approved SMN1 DNA delivered via AAV vector gene therapy indicated for pediatric spinal muscular atrophy (SMA)

Zynteglo

Zynteglo - FDA and EMA approved, autologous hematopoietic stem cells transduced with lentiglobin BB305 lentiviral vector encoding the β-globin gene derivative (βAT87Q-globin)

Oxlumo - FDA approved RNAi therapeutic for primary hyperoxaluria type 1 (PH1)

Skysona

Spikevax

Skysona - FDA approved, ex vivo transduction of functional ABCD1 genes with the Lenti-D lentiviral into the patient's hematopoietic stem cells for treatment of cerebral adrenoleukodystrophy (CALD)

Tecartus

Tegsedi

Viltepso

Vyondys 53

Tecartus - FDA approved CAR-T therapy for refractory B-cell precursor acute lymphoblastic leukemia

Tegsedi - FDA approved antisense oligonucleotide inhibitor of the transthyretin (TTR) protein for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis

Viltepso (Nippon Shinyaku) - FDA approved exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)

Vyondys 53 (Serepta Therapeutics) - FDA approved exon 53 skipping antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD)

Zolgensma - FDA approved AAV vector gene therapy indicated for pediatric spinal muscular atrophy

Zynteglo

Neovasculgen

NurOwn

Neovasculgen - Approved in Russia for peripheral artery disease

Oncorine - oncolyticOncolytic virus approved in China, indicated for nasopharyngeal carcinoma

Onpattro

Oxlumo

Onpattro - RNAi therapeutic approved in the United States and Canada for polyneuropathy of hATTR amyloidosis

Oxlumo - FDA approved RNAi therapeutic primary hyperoxaluria type 1 (PH1)

Imlygic - FDA-approvedFDA approved engineered human herpes simplex virus (HSV) as an oncolytic virus to treat advanced melanoma

Kymriah

Leqvio

Libmeldy

Kymriah - FDA approved CAR-T therapy for B cell acute lymphoma and follicular lymphoma

Leqvio - Approved in the UK to treat high cholesterol

Libmeldy - Approved in the UK to treat metachromatic leukodystrophy (MLD)

Luxterna - FDA-approvedFDA and Health Canada approved in-vivo AAV (Adeno-associated virus) gene therapy product for Leber congenital amaurosis (LCA)

Carteyva

Carvykti

Collategene

Comirnaty

Delytact

Carteyva - approved by the China National Medical Products Administration (NMPA) for large B cell lymphoma and follicular lymphoma

Carvykti - CAR-T therapy FDA approved for multiple myeloma

Collategene - approved in Japan to treat critical limb ischemia

Delytact - conditional approval in Japan for oncolytic virus therapy for brain cancer

Gendicine - approved in China for head and neck cancers

Givlaari

Givlaari - FDA approved to treat acute hepatic porphyria (AHP)

Invossa

Invossa - was approved in Korea and later suspended, for treatment of knee osteoarthritis

Abecma

Amondys 45

ARI-0001

Breyanzi

Abecma - CAR-T cell therapy for multiple melanomoa

Amondys 45 - Exon skipping therapy for Duchenne muscular dystrophy (DMD)

ARI-0001 - CAR-T therapy approved by the Spanish Agency for Medicines and Health Products (AEMPS) for acute lymphoblastic leukaemia

Breyanzi - CAR-T therapy for large B cell lymphoma

Gene Therapy usesis the use of genes or genetic material to treat or prevent disease. Types of gene therapy include replacing a mutated gene with a healthy copy, inactivating or knocking out a mutated gene or introducing a new gene to fight disease. Instead of delivering an entire gene, gene editing can deliver genetic material that edits DNA within a cell. In vivo gene therapy approaches directly introduce the gene therapy into the body. Ex vivo approaches in gene therapy first remove cells from the patient and genetic modification occurs outside the body, followed by reintroduction of cells back into the patient.

Most gene therapies use a viral vector to deliver genetic material into cells. Adeno-associated viruses (AAVs) are the most popular delivery systems for gene therapy in clinical trials as of 2022. Early- and late-stage clinical trials for hemophilia, inherited blindness and muscular dystrophy have been successful in terms of safety and efficacy. AAVs are non-pathogenic, have low immunogenicity, infect a broad range of cell types and are able to achieve efficient and long-lived gene transfer.

Gene Therapy uses genes or genetic material to treat or prevent disease. Types of gene therapy include replacing a mutated gene with a healthy copy, inactivating or knocking out a mutated gene or introducing a new gene to fight disease. Instead of delivering an entire gene, gene editing can deliver genetic material that edits DNA within a cell. In vivo gene therapy approaches directly introduce the gene therapy into the body. Ex vivo approaches in gene therapy first remove cells from the patient and genetic modification occurs outside the body, followed by reintroduction of cells back into the patient.

CRISPR-Cas9 is an RNA-guided genome editing tool, first used in mammalian organisms in 2013, that has become a cost-effective and convenient tool for gene therapy applications. CRISPR-Cas9 can be used to correct disease-causing mutations or engineer pathogens such as HIV for therapeutic purposes or introduce protective or therapeutic mutations.

The majority of gene therapies in clinical trials between 2010 and 2020 were for treatment of cancer. Ex-vivo gene therapy is an approach to developing immunotherapy. Immunotherapy with CAR TT-based cellsimmunotherapies isare generated by engineering T cells to express chimeric receptors on their surface, allowing them to react to specific molecules such as tumor-associated antigens.

The majority of gene therapies in clinical trials between 2010 and 2020 were for treatment of cancer. Ex-vivo gene therapy is an approach to developing immunotherapy. Immunotherapy with CAR T cells is generated by engineering T cells to express chimeric receptors on their surface, allowing them to react to specific molecules such as tumor-associated antigens.

Abecma

Amondys 45

ARI-0001

Breyanzi

Carteyva

Carvykti

Collategene

Comirnaty

Delytact

Gendicine for head and neck cancers

Givlaari

Imlygic - FDA-approved engineered human herpes simplex virus (HSV) as an oncolytic virus to treat advanced melanoma

Invossa

Kymriah

Leqvio

Libmeldy

Luxterna - FDA-approved in-vivo AAV (Adeno-associated virus) gene therapy product for Leber congenital amaurosis (LCA)

Neovasculgen

NurOwn

Oncorine - oncolytic virus indicated for nasopharyngeal carcinoma

Onpattro

Oxlumo

Skysona

Spikevax

Stremvelis - EMA approved, used ex vivo to treat combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID)

Tecartus

Tegsedi

Viltepso

Vyondys 53

Waylivra

Yescarta

Zolgensma - AAV vector indicated for pediatric spinal muscular atrophy

Adeno-associated viruses (AAVs) are the most popular delivery systems for gene therapy in clinical trials as of 2022. Early- and late-stage clinical trials for hemophilia, inherited blindness and muscular dystrophy have been successful in terms of safety and efficacy. AAVs are non-pathogenic, have low immunogenicity, infect a broad range of cell types and are able to achieve efficient and long-lived gene transfer.

AAV was originally discovered as a contaminant in simian adenovirus preparation, and was later found to integrate into the host genome during the latent state of the viral life cycle. For productive replication, AVV relies on co-infection with a helper virus such as adenovirus or herpes-virus. For gene transfer applications, the gene of interest is inserted into replication defective AAV viral-like particles (recombinant AAV or rAAV) in which viral open reading frames have been removed.

One challenge for AAV vector-based gene therapies is pre-existing humoral immunity to AAV capsids, antibodies to AAV present due to exposure to wild-type AAV, which are common in the environment. Patients are often excluded from clinical trials due to pre-existing neutralizing antibodies that might reduce transduction efficiency. Other challenges include poor transduction efficiency in certain tissues, low organ specificity and patients show vector dose-dependent toxicity. The high cost of production of rAAV is also an obstacle to its use in gene therapy.