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Titolo:
Antisense imaging of gene expression in the brain in vivo
Autore:
Shi, NY; Boado, RJ; Pardridge, WM;
Indirizzi:
Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 26, volume: 97, anno: 2000,
pagine: 14709 - 14714
SICI:
0027-8424(200012)97:26<14709:AIOGEI>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
EPIDERMAL GROWTH-FACTOR; PEPTIDE NUCLEIC-ACIDS; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDE; 3'-UNTRANSLATED REGION; RAT-BRAIN; IN-VIVO; BARRIER; TRANSPORTER; RECEPTORS; DELIVERY;
Keywords:
blood-brain barrier; transferrin receptor; monoclonal antibody; peptide nucleic acid;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Pardridge, WM Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 A 90095 USA
Citazione:
N.Y. Shi et al., "Antisense imaging of gene expression in the brain in vivo", P NAS US, 97(26), 2000, pp. 14709-14714

Abstract

Antisense radiopharmaceuticals could be used to image gene expression in the brain in vivo, should these polar molecules be made transportable through the blood-brain barrier. The present studies describe an antisense imaging agent comprised of an iodinated peptide nucleic acid (PNA) conjugated to a monoclonal antibody to the rat transferrin receptor by using avidin-biotin technology. The PNA was a 16-mer antisense to the sequence around the methionine initiation codon of the luciferase mRNA. C6 rat glioma cells were permanently transfected with a luciferase expression plasmid, and C6 experimental brain tumors were developed in adult rats. The expression of the luciferase transgene in the tumors in vivo was confirmed by measurement of luciferase enzyme activity in the tumor extract. The [I-125]PNA conjugate was injected intravenously in anesthetized animals with brain tumors and killed 2 h later for frozen sectioning of brain and film autoradiography. No imageof the luciferase gene expression was obtained after the administration ofeither the unconjugated antiluciferase PNA or a PNA conjugate that was antisense to the mRNA of a viral transcript. In contrast, tumors were imaged in all rats administered the [I-125]PNA that was antisense to the luciferasesequence and was conjugated to the targeting antibody. In conclusion, these studies demonstrate gene expression in the brain in vivo can be imaged with antisense radiopharmaceuticals that are conjugated to a brain drug-targeting system.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 02:58:29