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The Horizon of Gene Therapy in Modern Medicine: Advances and Challenges

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Cell Biology and Translational Medicine, Volume 8

Part of the book series: Advances in Experimental Medicine and Biology ((CBTMED,volume 1247))

Abstract

Gene therapy as a novel study in molecular medicine will have a significant impact on human health in the near future. In recent years, the scope of gene therapy has been developed and is now beginning to revolutionize therapeutic approaches. Accordingly, many types of diseases are now being studied and treated in clinical trials through various gene delivery vectors. The emergence of recombinant DNA technology which provides the possibility of fetal genetic screening and genetic counseling is a good case in point. Therefore, gene therapy advances are being applied to correct inherited genetic disorders such as hemophilia, cystic fibrosis, and familial hypercholesterolemia as well as acquired diseases like cancer, AIDS, Alzheimer’s disease, Parkinson’s disease, and infectious diseases like HIV. As a result, gene therapy approaches have the ability to help the vast majority of newborns with different diseases. Since these ongoing treatments and clinical trials are being developed, many more barriers and challenges have been created. In order to continue this positive growth, these challenges need to be recognized and addressed. Accordingly, safety, efficiency and also risks and benefits of gene therapy trials for each disease should be considered. As a result, sustained manufacturing of the therapeutic gene product without any harmful side effects is the least requirement for gene therapy. Herein, different aspects of gene therapy, an overview of the progress, and also the prospects for the future have been discussed for the successful practice of gene therapy.

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Abbreviations

BMT:

Bone Marrow Transplant

G-CSF :

Granulocyte-Colony Stimulating Factor

HCT:

Hematopoietic Cell Transplantation

HSC:

Hematopoietic Stem Cell

HSCT:

Hematopoietic Stem Cell Transplantation

CRISPR/Cas9:

Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9

RNAi:

RNA interference

PIDs:

Primary Immune Deficiencies

SCID:

Severe Combined Immunodeficiency

SCID-X1:

X-linked Severe Combined Immunodeficiency

ADA-SCID:

Adenosine Deaminase deficient Severe Combined Immunodeficiency

CGD:

Chronic Granulomatous Disease

WAS:

Wiskott – Aldrich Syndrome

WASP:

Wiskott – Aldrich syndrome Protein

ALD:

Adrenoleukodystrophy

MLD:

Metachromatic Leukodystrophy

gp91phox :

Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2

ABCD1:

ATP Binding Cassette Subfamily D Member 1

ARSA:

Arylsulfatase A

IL2RyC :

Interleukin 2 Receptor

CCR5:

C-C Chemokine Receptor type 5

SB-transposon:

Sleeping Beauty (SB) transposon

Anti-CD19 CAR:

Anti-CD19 Chimeric Antigen Receptor

SIN-lentiviral:

Self-Inactivating (SIN) lentiviral vector

LDL receptor:

Low-Density Lipoprotein Receptor

P53 (TP53):

Tumor Protein P53

LPLD:

Lipoprotein Lipase Deficiency

SERCA2a:

Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase

RPE65:

Retinal Pigment Epithelium-specific 65

GAD:

Glutamate Decarboxylase

FIX:

Factor IX Padua

ASPA:

Aspartoacylase

LPL:

Lipoprotein lipase

CNS:

Central Nervous System

SMA:

Spinal Muscular Atrophy

LCA:

Leber Congenital Amaurosis

LCA2:

LCA type 2

SCA:

Sickle Cell Anaemia

CF:

Cystic Fibrosis

CFTR:

Cystic Fibrosis Transmembrane Regulator

DSB:

Double Stranded Break

HDR:

Homology Directed Repair

NHEJ:

Non-Homologous End Joining

MN:

Meganuclease

ZFNs:

Zinc-Finger Nucleases

ZFPs:

Zinc Finger Proteins

TALE:

Transcription Activator Like Effector

TALENs:

Transcription Activator-Like Effector Nucleases

PAM:

Protospacer Adjacent Motif

HBB:

Hemoglobin subunit Beta

HPV:

Human Papillomaviruses

HIV:

Human Immunodeficiency Virus

HBV:

Hepatitis B virus

ALL:

Acute Lymphoblastic Leukemia

GGE:

Germline Gene Editing

DDR:

DNA Damage Response

ICL:

Interstrand Crosslink

BER:

Base Excision Repair

NER:

Nucleotide Excision Repair

TC-NER:

Transcription-Coupled NER

GG-NER:

Global Genome NER

MMR:

Mismatch Repair

HR:

Homologous Recombination

ROS:

Reactive Oxygen Species

NO:

Nitric Oxide

UV:

Ultraviolet light

CPDs:

Cyclobutane Pyrimidine Dimers

PAH:

Polycyclic Aromatic Hydrocarbon

AGTs:

O6-Alkylguanine-DNA Alkyltransferases

MSH:

MutS Homolog

MLH/PMS:

MutL Homolog/ Premenstrual Syndrome

TLS:

Translesion Synthesis

AEP:

Archaeo-Eukaryotic Primase

alt-EJ:

alternative End Joining

SSA:

Single-Strand Annealing

TGE:

Transient Gene Expression

R-proteins:

Recombinant Proteins

HEK:

Human Embryonic Kidney

CHO:

Chinese Hamster Ovary

CMV:

Cytomegalovirus

HCMV:

Human Cytomegalovirus

EBNA-1:

Epstein–Barr virus Nuclear Antigen-1

VLPs:

Virus-Like Particles

BEVS:

Baculovirus Expression Vector System

PEI:

Polyethylenimine

ds:

double-stranded

ss:

single-stranded

AAV:

Adeno Associated Viruses

rAAV:

recombinant Adeno Associated Virus

LV:

Lentiviral

IBCs:

Institutional Biosafety Committees

NIH:

National Institutes of Health

RAC:

Recombinant DNA Advisory Committee

BSL:

Biosafety Level

CBER:

Center for Biologics Evaluation and Research

cGMP:

current Good Manufacturing Practices

IND:

Investigational New Drug

GLP:

Good Laboratory Practice

RODAC:

Replicate Organism Detection and Counting

DMD:

Duchenne Muscular Dystrophy

T1DM:

Type 1 Diabetes Mellitus

T2DM:

Type 2 Diabetes Mellitus

CFR:

Code of Federal Regulations

IGF1:

Insulin-like Growth Factor 1

HGF gene:

Hepatocyte Growth Factor gene

Reg3g:

Regenerating islet-derived protein 3 gamma gene

G6Pase:

Glucose-6-Phosphatase

SAEs:

Serious Adverse Events

OTC:

Ornithine Transcarbamylase

OTCD:

Ornithine Transcarbamylase Deficiency

ATMPs:

Advanced therapy medicinal products

GTMP:

Gene Therapy Medicinal Products

sCTMPs:

somatic Cell Therapy Medicinal Products

TEPs:

Tissue-Engineered Products

MMA:

Marketing Authorization Application

CAT:

Committee for Advanced Therapies

FDA:

Food and Drug Administration

IND:

Investigational New Drug

OCTGT:

Office of Cellular, Tissue and Gene Therapy

CHMP:

Committee for Medicinal Products for Human Use

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Acknowledgements

The authors would like to thank Dr. Mohsen Khorshidi and Dr. Seyed Majid Manavi for their kind support.

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Authors and Affiliations

  1. Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Babak Arjmand, Mobina Amanollahi Baharvand & Negin sadat Hoseini Mohammadi

  2. Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Babak Arjmand, Motahareh Sheikh Hosseini & Peyvand Parhizkar Roudsari

  3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical sciences, Tehran, Iran

    Bagher Larijani

  4. Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Moloud Payab

  5. Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

    Kambiz Gilany

  6. Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran

    Kambiz Gilany

  7. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Parisa Goodarzi

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  1. Babak Arjmand
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  2. Bagher Larijani
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  8. Mobina Amanollahi Baharvand
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  9. Negin sadat Hoseini Mohammadi
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Correspondence to Babak Arjmand .

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  1. Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Kursad Turksen

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Arjmand, B. et al. (2019). The Horizon of Gene Therapy in Modern Medicine: Advances and Challenges. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 8. Advances in Experimental Medicine and Biology(), vol 1247. Springer, Cham. https://doi.org/10.1007/5584_2019_463

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