Leinster's inexperienced fly-half Joey Carbery could make his Test debut when Ireland attempt to stop New Zealand extending their record match-winning streak in Chicago on Saturday (8pm Irish time).
Carbery has just nine senior Leinster appearances to his name and turns 21 on 1 November, but could now take a seat on Ireland's bench for Saturday's autumn Test opener against the double world champions.
Ulster's Paddy Jackson will miss the USA trip due to personal reasons, leaving prodigious talent Carbery the most likely understudy to Johnny Sexton.
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Ireland must also bid to deny New Zealand a 19th consecutive victory without influential forwards Sean O'Brien, Iain Henderson and Peter O'Mahony.
"Players returning to full fitness Sean O'Brien, Iain Henderson and Peter O'Mahony along with Paddy Jackson, unavailable due to personal reasons, will not make the trip to Chicago," the Irish Rugby Football Union (IRFU) confirmed in a statement.
Sexton should start Saturday's Soldier Field clash, with Leinster team-mate Carbery now likely to take a seat on the bench in Ulster playmaker Jackson's absence.
Carbery has been promoted to Ireland's senior squad for the autumn series ahead of Ian Madigan, now plying his trade in Bordeaux.
Ireland would ideally have aimed to ease the Leinster academy graduate's transition, but his form in the Guinness PRO12 suggests he boasts the requisite skills to cope in the Test arena.
Leinster flanker O'Brien has only just returned from long-term hamstring trouble, and has been deemed not quite ready for Test rugby.
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Ireland will hope the combative loose-forward will be available for selection by the time they face New Zealand again, in Dublin on 19 November.
Peter O'Mahony has recently beaten the knee ligament problem that ended his World Cup 2015 campaign prematurely in the 24-9 pool stage victory over France.
As with O'Brien, Ireland are taking few risks with the Munster captain in the hope the 27-year-old can be at full tilt by the time New Zealand pitch up in Dublin.
Powerful back-five forward Henderson suffered a shoulder injury in Ulster's 19-18 Champions Cup victory over Exeter Chiefs on 22 October.
Ireland remain hopeful the 24-year-old can make a quick recovery to play a meaningful part in what will be another gruelling November series.
Munster forward Donnacha Ryan said: “This is the pinnacle of professional rugby and you want to play the best in the world. Obviously playing it over in Chicago is an added thrill as well.
“We’ve got to be prepared because they are on a massive [18-game winning] streak at the moment.”
James Tracy and Luke Marshall, along with the suspended Keith Earls, are the others left off the travelling party from the extended squad named last week.
The 27-man squad departed from Dublin Airport this afternoon and is due to land in the early hours of Tuesday morning (Irish time).
Finlay Bealham (Buccaneers/Connacht)
Rory Best (Banbridge/Ulster) (captain)
Joey Carbery (Clontarf/Leinster)*
Sean Cronin (St Marys/Leinster)
Ultan Dillane (Corinthians/Connacht)
Tadgh Furlong (Clontarf/Leinster)
Craig Gilroy (Ulster)
Cian Healy (Clontarf/Leinster)
Jamie Heaslip (Dublin University/Leinster) (vice captain)
Robbie Henshaw (Buccaneers/Leinster)
Billy Holland (Cork Constitution/Munster)*
Rob Kearney (UCD/Leinster)
Kieran Marmion (Buccaneers/Connacht)
Jack McGrath (St Marys/Leinster)
Luke McGrath (UCD/Leinster)*
Jordi Murphy (Lansdowne/Leinster)
Conor Murray (Garryowen/Munster)
Jared Payne (Ulster)
Garry Ringrose (UCD/Leinster)*
Donnacha Ryan (Shannon/Munster)
John Ryan (Cork Constitution/Munster)*
Jonathan Sexton (St Marys/Leinster)
CJ Stander (Munster)
Devin Toner (Lansdowne/Leinster)
Andrew Trimble (Ballymena/Ulster)
Josh van der Flier (UCD/Leinster)
Simon Zebo (Cork Constitution/Munster).