Specific gene blockade shows that peptide nucleic acids readily enter neuronal cells in vivo

FEBS Letters

Hoshall, Clark V²  Jansen, Karen²  Cusack, Bernadette²  Douglas, Christopher L²  Tyler, Beth M²  Lacy, Benjamin W²  Richelson, Elliott²  McCormick, Daniel J¹ 

[1] Biochemistry and Molecular Biology, Mayo Clinic, 200 First St., SW, Rochester, MN 55905, USA;Neuropsychopharmacology, Mayo Clinic, Birdsall Medical Research Building, 4500 San Pablo Rd., Jacksonville, FL 32224, USA

关键词: Peptide nucleic acid;    Neurotensin;    Morphine;    Antinociception;    Hypothermia;    PNA;    peptide nucleic acid;    NT;    neurotensin;    NTR;    neurotensin receptor;    MPE;    maximum physiological effect;    PAG;    periaqueductal gray;   

DOI  :  10.1016/S0014-5793(97)01575-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Peptide nucleic acids (PNAs) are DNA analogs that can hybridize to complementary sequences with high affinity and stability. Here, we report the first evidence of intracellular delivery of PNAs in vivo. Two CNS receptors, an opioid (mu) and a neurotensin (NTR-1), were targeted independently by repeated microinjection of PNAs into the periaqueductal gray. Behavioral responses to neurotensin (antinociception and hypothermia) and morphine (antinociception) were lost in a specific manner. Binding studies confirmed a large reduction in receptor sites. The loss of behavioral responses was long lasting but did fully recover. The implications of specifically and readily turning off gene expression in vivo are profound.

【 授权许可】

Unknown