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                                                                   EXHIBIT 10.55


                            FIFTH AMENDMENT TO LEASE


      This Fifth Amendment to Lease is entered into by and between CHARLES RIVER
BUILDING LIMITED PARTNERSHIP, a Delaware limited partnership, with an address of
875 North Michigan Avenue, Suite 1350, Chicago, Illinois 60611 ("Landlord") and
HYBRIDON, INC., a Delaware corporation, with an address of 620 Memorial Drive,
Cambridge, Massachusetts 02139 ("Tenant").

      Reference is hereby made to that certain Lease between Landlord and Tenant
dated February 4, 1994, as amended by a certain First Amendment to Lease dated
as of November 30, 1995 (the "First Amendment"), a certain Second Amendment to
Lease dated as of February 23, 1996 (the "Second Amendment"), a certain Third
Amendment to Lease dated as of February 28, 1996 (the "Third Amendment"), and a
certain Fourth Amendment to Lease between Landlord and Tenant dated as of July
25, 1996 (the "Fourth Amendment") (collectively, the "Lease"). Capitalized terms
used herein and not otherwise defined shall have the meanings given them in the
Lease.

      WHEREAS, Landlord and Tenant wish to amend the Lease on the terms and
conditions hereinafter set forth.

      NOW, THEREFORE, for good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, Landlord and Tenant hereby agree
that as of the date hereof, the Lease is amended as follows:

      Notwithstanding anything to the contrary set forth in the Lease,
including, without limitation, Article X entitled "Option to Purchase" Tenant
shall have the right and option to purchase the Premises for a purchase price
equal to the greater of (i) the "Fair Market Value" (as defined in said Article
X of the Lease); and (ii) the aggregate amount outstanding under any first
mortgage loan encumbering the Premises, including, without limitation, all
outstanding principal, accrued and unpaid interest, late fees and charges,
default interest, and any yield maintenance and prepayment penalties and fees
outstanding on the date of the exercise of such purchase option. Tenant further
agrees that its option to purchase the Premises as set forth in the Lease is
fully and unconditionally subordinated to the terms and conditions of any such
first mortgage encumbering the Premises now existing or hereafter placed on the
Premises and that said option to purchase shall be automatically and irrevocably
terminated and canceled upon any foreclosure of said mortgage or the recording
by the holder thereof of a deed in lieu of foreclosure. The cancellation and
termination of such purchase option shall be automatic upon any foreclosure or
recording of a deed in lieu of foreclosure regardless of whether Tenant is in
default under the Lease and without the necessity of any further amendments or
modifications to the Lease. Notwithstanding the foregoing, however, the holder
of said mortgage shall notify Tenant of its intention to foreclose or to record
a deed in

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lieu of foreclosure with respect to the Premises and Tenant shall have thirty
(30) days from the date of receipt of said notice to exercise its option to
purchase the Premises for the amount set forth herein. An affidavit signed by
the holder of said mortgage recorded in the chain of title to the Premises shall
be conclusive and binding evidence that the said holder of said mortgage gave
the required notice to Tenant and that Tenant elected not to exercise its option
to purchase the Premises.

      EXECUTED as a sealed instrument as of the 14th day of March, 1997.

                                    LANDLORD:

                                    CHARLES RIVER BUILDING LIMITED
                                    PARTNERSHIP, a Delaware limited
                                    partnership
 

                                    By:   Pillar Development and Management,
                                          Inc., a Delaware corporation


                                          By: /s/ Robert Harte
                                             -------------------------------   
                                             Title:  Vice President



                                    TENANT:

                                    HYBRIDON, INC., a Delaware corporation


                                    By: /s/ E. Andrews Grinstead, III
                                       -------------------------------------
                                          Title:  Chairman, President & CEO






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