Therapeutic Potential of Gene Transfer to Testis; Myth or Reality?

Kojima, Yoshiyuki; Mizuno, Kentaro; Umemoto, Yukihiro; Sasaki, Shoichi; Hayashi, Yutaro; Kohri, Kenjiro

doi:10.5772/20488

Cited by 3 publications

(9 citation statements)

References 102 publications

(89 reference statements)

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“…Leydig cells are also a potential gene therapy. Their dysfunction can lead to infertility, which is believed to be one of the mechanisms of infertility in Kleinfelter (47XXY) syndrome [40,64]. Marker genes expressed involved in spermatogenesis that are expressed by Leydig cells have been identified [40,65].…”

Section: Future Of Gene Therapy Techniques and The Treatment Of Male mentioning

confidence: 99%

“…Retroviral vectors were found to introduce transgenes into the germ line and spermatogonia in vitro [56] and in vivo [57]. Lentiviral vector use in basic science research has been increasing due to its capacity to efficiently transduce cells with long-term gene expression using large-sized DNA [40]. They can infect both dividing and nondividing cells.…”

Section: Viral Vectors For Gene Therapymentioning

confidence: 99%

“…Nonviral vectors are advantageous in that they are cheap, have no DNA size limitations, and have a good safety profile [40]. However, expression of genes is short term and transfection efficiency is often low.…”

Section: Gene Therapy Using Nonviral Vectorsmentioning

confidence: 99%

“…Abnormalities in the maturation of Sertoli cells may lead to testicular dysfunction. Therefore, understanding expression patterns of genes that signify Sertoli cell maturity such as anti-Mullerian hormone, vimentin, aromatase, and inhibin alpha my provided a basis for gene therapy-based interventions [40]. Dysfunction of transcriptional regulation due to defective transcription factors (such as CREB, Sox3, PEM, and DAX1) may result in male infertility [40].…”

Section: Future Of Gene Therapy Techniques and The Treatment Of Male mentioning

confidence: 99%

“…Adenoviral vectors are most commonly used. They are able to infect dividing and differentiated cells and tend not to integrate into the host genome [40]. Using adenovirus vectors, transgenes were transferred to animal testes in vivo.…”

Section: Viral Vectors For Gene Therapymentioning

confidence: 99%

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Future Perspectives in the Diagnosis and Management of Unexplained Male Infertility

Maganty

Ramasamy

2015

Unexplained Infertility

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Section: Future Of Gene Therapy Techniques and The Treatment Of Male mentioning

confidence: 99%

Section: Viral Vectors For Gene Therapymentioning

confidence: 99%

Section: Gene Therapy Using Nonviral Vectorsmentioning

confidence: 99%

Section: Future Of Gene Therapy Techniques and The Treatment Of Male mentioning

confidence: 99%

Section: Viral Vectors For Gene Therapymentioning

confidence: 99%

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Future Perspectives in the Diagnosis and Management of Unexplained Male Infertility

Maganty

Ramasamy

2015

Unexplained Infertility

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Connexin 43 a check-point component of cell proliferation implicated in a wide range of human testis diseases

Chevallier

Carette

Segretain

et al. 2012

Cell. Mol. Life Sci.

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Gap junction channels link cytoplasms of adjacent cells. Connexins, their constitutive proteins, are essential in cell homeostasis and are implicated in numerous physiological processes. Spermatogenesis is a sophisticated model of germ cell proliferation, differentiation, survival, and apoptosis, in which a connexin isotype, connexin 43, plays a crucial role as evidenced by genomic approaches based on gene deletion. The balance between cell proliferation/differentiation/apoptosis is a prerequisite for maintaining levels of spermatozoa essential for fertility and for limiting anarchic cell proliferation, a major risk of testis tumor. The present review highlights the emerging role of connexins in testis pathogenesis, focusing specifically on two intimately interconnected human testicular diseases (azoospermia with impaired spermatogenesis and testicular germ cell tumors), whose incidence increased during the last decades. This work proposes connexin 43 as a potential cancer diagnostic and prognostic marker, as well as a promising therapeutic target for testicular diseases.

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NLC Delivery of EGFP Plasmid to TM4 Cell Nuclei for Targeted Gene Therapy

Jummah,

Satrialdi,

Artarini

et al. 2024

Adv Pharm Bull

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Purpose: This study evaluated whether a nanostructured lipid carrier (NLC) delivery system could safely and accurately deliver nucleic acids to the cell nucleus using the enhanced green fluorescent protein (EGFP)-C1 plasmid model. Methods: The NLC was formulated using the emulsification method and equipped for cationic lipid-mediated transfection with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), which interacts electrostatically with nucleic acid. The NLC attributes, including size, polydispersity index, and zeta potential, were assessed by dynamic light scattering. The morphological structure was analyzed using transmission electron microscopy. Entrapment efficiency was evaluated by a direct method. Cellular uptake mechanisms of pEGFP-C1-NLC and the ability of pEGFP-C1 to penetrate the nucleus of TM4 cells to express EGFP were observed using confocal microscopy. Results: pEGFP-C1-NLC exhibited particle sizes in the range 56-88 nm with a particle charge range of -6.0 to +1.3 mV. The polydispersity index <0.5 showed good size uniformity, and entrapment efficiency of pEGFP-C1in the NLC was 92.06 ± 2.295%. The NLC formulation was internalized predominantly via caveolae-mediated endocytosis, as indicated by EGFP expression following successful delivery of pEGFP by the NLC into the cells. Conclusion: NLC formulation could deliver genetic material to the nucleus and could be considered a gene therapy candidate for spermatogenesis.

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Therapeutic Potential of Gene Transfer to Testis; Myth or Reality?

Cited by 3 publications

References 102 publications

Future Perspectives in the Diagnosis and Management of Unexplained Male Infertility

Future Perspectives in the Diagnosis and Management of Unexplained Male Infertility

Connexin 43 a check-point component of cell proliferation implicated in a wide range of human testis diseases

NLC Delivery of EGFP Plasmid to TM4 Cell Nuclei for Targeted Gene Therapy

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