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  APPLICATIONS OF PEPTIDES NUCLEIC ACIDS (PNA) IN MOLECULAR MEDICINE AND BIOTECHNOLOGYFREEfree


Minerva Biotecnologica 1999 September;11(3):187-92

Copyright © 1999 EDIZIONI MINERVA MEDICA

lingua: Inglese

Antisense oligonucleotides and PNAs for sequence-specific regulation of gene expression

Ferrari S.

Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università degli Studi - Modena e Reggio Emilia, Italy


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It has ­become increas­ing­ly ­clear in ­recent ­years ­that ­there are ­many pos­sible reg­u­la­to­ry ­steps in the path­way ­from ­gene to pro­tein: chrom­a­tin con­for­ma­tion and tran­scrip­tion­al con­trol; ­post-tran­scrip­tion­al reg­u­la­tion, par­tic­u­lar­ly splic­ing, mRNA stabil­ity, nucle­ar cyto­plasm trans­port of mRNAs, nat­u­ral anti­sense tran­scripts; trans­la­tion­al and ­post-trans­la­tion­al con­trol. Using anti­sense strat­e­gies it is pos­sible to inter­fere ­with ­most of the reg­u­la­to­ry mech­a­nisms under­ly­ing ­gene expres­sion ­both in embryon­ic and somat­ic ­cells. The spe­cif­ic ­gene inac­ti­va­tion in a par­tic­u­lar cel­lu­lar con­text is the nec­es­sary ­step to eval­u­ate its pos­sible bio­log­i­cal func­tion. Several dif­fer­ent tech­ni­cal approach­es ­based on dif­fer­ent meth­o­dol­o­gies under­lie anti­sense strat­e­gies. Among ­these, anti­sense oli­go­nu­cleo­tides and pep­tide nucle­ic ­acids (PNAs) are con­sid­ered in ­this ­short ­review. In ­these experi­men­tal approach­es it is essen­tial to iden­ti­fy the tar­get ­genes and the ­most suit­able cel­lu­lar ­system. In ­fact, ­gene inac­ti­va­tion in somat­ic ­cells ­allows us to ­study ­basic ques­tions in ­cell biol­o­gy, ­such as ­cell ­cycle reg­u­la­tion, dif­fe­ren­ti­a­tion apop­to­sis, ­cell acti­va­tion, cel­lu­lar trans­for­ma­tion, with­out hav­ing to strug­gle ­with the com­plex­ities of ani­mal mod­els. We ­have stud­ied the bio­log­i­cal con­se­quenc­es of c-myb, c-fes and Bax ­genes inac­ti­va­tion in nor­mal and leu­kem­ic mye­loid ­cells and ­their pos­sible ther­a­peu­tic appli­ca­tions. New deliv­ery ­systems, ­based on trans­lo­cat­ing pep­tides to effi­cient­ly pen­e­trate the ­cells ­with anti­sense oli­go­nu­cleo­tides, PNAs and bio­log­i­cal­ly ­active pep­tides are ­also dis­cussed.

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