Inder Verma<\/a>, a professor of genetics at Salk and senior author of the study appearing in today’s Proc. Natl. Acad. Sci. “Most of those cases are not due to defects in sperm cells themselves, but in other cells that support sperm production.”<\/p>\nThe mice in the study had mutations in a gene called KL2 (for c-kit ligand 2) in their Sertoli cells, cells in the testis that aid in sperm cell development by providing structural support and growth factors. The mutant mice failed to make sperm.<\/p>\n
Functional KL2 genes were delivered to the mice using lentiviral vectors, based on a crippled version of HIV that was first developed by Verma and Salk Institute colleagues in 1996. Treatment with the vectors restored sperm production to substantial levels in all nine animals treated, without inducing any discernable side effects.<\/p>\n
Sperm cells from the treated mice were tested for their ability to generate offspring. While not enough sperm could be collected to carry out normal in vitro fertilization, in which sperm and eggs are simply mixed together, a procedure known as assisted fertilization was successful. Fertilized embryos appeared to develop normally in vitro, and healthy pups were born from some implanted females.<\/p>\n
“Assisted fertilization involves microinjecting spermatozoa directly into eggs,” said Masahito Ikawa, a postdoctoral fellow in Verma’s lab and first author on the study. “It’s an accepted technique for helping men with low sperm counts.<\/p>\n
“But most men with fertility problems don’t make viable sperm at all or make too little for even assisted fertilization to work,” he added. “For them, the gene therapy approach may eventually offer another option.”<\/p>\n
None of the offspring tested positive for the presence of the normal KL2 gene carried by the gene therapy vector.<\/p>\n
“This result indicates that the vectors transduced the Sertoli cells only, and not the actual spermatozoa,” said Verma. “It’s an important point, because a high level of concern exists about making permanent alterations to a patient’s germ line that would be perpetuated to his descendants.<\/p>\n
“The current result suggests we may, in fact, be able to treat male infertility using gene therapy without worrying about those types of consequences.”<\/p>\n
Salk co-authors include Vinay Tergaonkar, a postdoctoral fellow in Verma’s laboratory. Additional authors include Atsuo Ogura, Narumi Ogonuki and Kimiko Inoue at The Institute of Physical and Chemical Research (RIKEN) in Tsukuba, Japan. The study, titled “Restoration of spermatogenesis by lentiviral gene transfer: Offspring from infertile mice,” was funded by the National Institutes of Health, the March of Dimes Birth Defects Foundation, the Wayne and Gladys Valley Foundation, and the H. N. and Frances C. Berger Foundation. Verma is an American Cancer Society Professor of Molecular Biology. Ikawa is supported by the Valley Foundation and Terganokar is supported by a fellowship from the Leukemia and Lymphoma Society.<\/p>\n
El Instituto Salk de Estudios Biol\u00f3gicos, ubicado en La Jolla, California, es una instituci\u00f3n independiente sin fines de lucro dedicada a descubrimientos fundamentales en las ciencias de la vida, la mejora de la salud y las condiciones humanas, y la formaci\u00f3n de futuras generaciones de investigadores. El Instituto fue fundado en 1960 por Jonas Salk, M.D., con un donativo de terrenos de la Ciudad de San Diego y el apoyo financiero de la March of Dimes Birth Defects Foundation.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[115],"disease-research":[],"class_list":["post-2164","disclosure","type-disclosure","status-publish","hentry","faculty-inder-verma"],"acf":[],"yoast_head":"\n
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