Exhibit 10.34


                 FIFTH AMENDMENT TO LOAN AND SECURITY AGREEMENT


        This Fifth  Amendment is made,  effective as of the 4th day of December,
1998,  to that certain Loan and Security  Agreement  between  Hybridon,  Inc., a
Delaware  corporation  with  a  principal  place  of  business  at  155  Fortune
Boulevard, Milford, Massachusetts (the "Borrower"), and Silicon Valley Bank (the
"Bank")  dated as of  December  31,  1996,  as  amended.  The Loan and  Security
Agreement,  as  amended  to  date,  is  hereinafter  referred  to as  the  "Loan
Agreement." Capitalized terms used but not defined in this Fifth Amendment shall
have the meanings ascribed to them in the Loan Agreement,  or if not so defined,
shall have the meanings  ascribed to them in the Uniform  Commercial Code, or in
the case of  financial  and  accounting  terms,  in  accordance  with  generally
accepted accounting principles.

        Pursuant to the Loan Agreement and on the terms and conditions set forth
therein, on December 31, 1996, the Bank made a secured term loan to the Borrower
in the original  face amount of $7,500,000  (the "Loan").  On November 24, 1998,
Forum Capital Markets,  LLC ("Forum")  purchased the Bank's entire right,  title
and interest in and to the Loan,  including all  principal and unpaid  interest,
which at such time was in the  principal  amount of  $2,769,789.  Pursuant  to a
Purchase  and  Assignment  Agreement  dated  November  24, 1998  between  Forum,
Delaware State  Employees  Retirement Fund  ("Delaware  State"),  Declaration of
Trust for the Defined  Benefit  Plans of ICI  American  Holdings  Inc.  ("ICI"),
Declaration  of Trust for the  Defined  Benefit  Plans of Zeneca  Holdings  Inc.
("Zeneca"),  The J.W. McConnell Family Foundation ("McConnell"),  General Motors
Employees Domestic Group Trust ("GM"),  and Thermo Electron Balanced  Investment
Fund ("Thermo Electron") (Delaware State, ICI, Zeneca,  McConnell, GM and Thermo
Electron being hereinafter  referred to collectively as the "Pecks  Investors"),
Forum agreed to advance an additional $280,706 and the Pecks Investors agreed to
advance an  additional  $2,949,505 to the  Borrower,  and Forum  assigned to the
Pecks  Investors  a one-half  interest  in and to the Loan.  Forum and the Pecks
Investors are hereinafter  referred to together as the "Lenders." On December 1,
1998,  Forum advanced an additional  $280,706 to the Borrower and on December 4,
1998 the Pecks  Investors  advanced  the  following  additional  amounts  to the
Borrower:

               Delaware State               $1,838,249.32
               ICI                          $1,304,388.92
               Zeneca                       $1,203,810.80
               McConnell                    $1,134,497.42
               GM                           $1,134,551.01
               Thermo Electron              $1,133,907.53

Such  additional  amounts from Forum and the Pecks  Investors have increased the
aggregate outstanding principal amount of the Loan to $6,000,000.

        In consideration of the undertakings and obligations of the Borrower and
the Bank set forth  herein and for other good and  valuable  consideration,  the
receipt and sufficiency of which are hereby  acknowledged,  the Borrower and the
Lenders hereby agree as follows:


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        1. The term  "Business  Day" shall be amended to refer to  Massachusetts
instead of California.

        2. The term "Maturity Date" shall be amended to mean November 30, 2003.

        3. Effective as of November 24, 1998, the term "Interest  Rate" shall be
amended to mean 8% per  annum,  which  shall be,  beginning  on such  date,  the
effective  interest rate on the  Borrower's  obligations in respect of the Loan,
notwithstanding  anything to the contrary in the Loan Agreement, as amended. The
Loan Agreement,  as amended, is hereby amended to delete any requirement therein
that the  Borrower  make any  additional  payments  to the Lender or the Bank in
excess of the interest and principal payments set forth in this Fifth Amendment.

        4. The amortization schedule of the Loan set forth in the Loan Agreement
shall be revised as follows:  no principal  shall be due until November 30, 2003
(unless the Obligations  shall become  immediately due and payable under Section
9.1 of the Loan Agreement).  Interest shall be payable monthly in arrears on the
last day of the month (or if such day is not a Business  Day, the next  Business
Day to occur).

        5. Section 6.9 of the Loan Agreement,  as amended,  is hereby amended to
read as follows:

               6.9   Minimum Liquidity.  Borrower shall maintain, as of the last
               calendar_day of each month,  Minimum Liquidity of Two Million and
               No/100 Dollars ($2,000,000.00). "Minimum Liquidity" is defined as
               consolidated  cash on hand  (other  than  cash in which an entity
               other  than  the  Lenders  or  their  assignees  has  a  security
               interest) (and cash  equivalents and marketable  securities) plus
               50% of accounts receivable.

        6. Section 10 of the First Amendment to the Loan and Security  Agreement
effective as of March 30, 1998, is hereby deleted.

        7. The Loan may not be prepaid,  in whole or in part,  at any time prior
to December 1, 2000, without the prior written consent of a majority in interest
of the Lenders.

        8. The principal  amount of the Loan, from time to time, and accrued but
unpaid interest thereon, shall be convertible,  in whole or in part, at Lender's
option,  into Common Stock of the  Borrower at a  conversion  price of $2.40 per
common share  (appropriately  adjusted for stock splits, stock dividends and the
like).

        9. All defaults and events of default which may exist on the date hereof
under the Loan Agreement are hereby waived.

        10. To the extent  possible,  this Fifth Amendment shall be construed to
be consistent with the provisions of the Loan Agreement;  however, to the extent
that  the  provisions  of  this  Fifth  Amendment  expressly  conflict  with  or
contradict  the provisions of the Loan  Agreement,  the provisions of this Fifth
Amendment shall be deemed to control.


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        11. This Fifth  Amendment  represents the entire  agreement  between the
parties  with  respect  to the  modifications  contained  herein,  and  shall be
construed in accordance with the laws of the Commonwealth of Massachusetts as an
agreement  under seal.  The  Borrower  has  voluntarily  entered into this Fifth
Amendment  without  coercion  or  duress of any kind and has been or has had the
opportunity to have been represented by legal counsel of their choosing.

        WITNESS OUR hands and seals on this 4th day of December, 1998.

HYBRIDON, INC.                              FORUM CAPITAL MARKETS, LLC


By:  /s/ E. Andrews Grinstead, III          By:  /s/ C. Keith Hartley
     -----------------------------               --------------------


                                            DELAWARE STATE EMPLOYEES
                                                 RETIREMENT FUND
                                            DECLARATION OF TRUST FOR THE
                                                 DEFINED BENEFIT PLANS OF ICI
                                                 AMERICAN HOLDING INC.
                                            DECLARATION OF TRUST FOR THE
                                                 DEFINED BENEFIT PLANS OF
                                                 ZENECA HOLDINGS INC.
                                            THE J.W. McCONNELL FAMILY
                                                 FOUNDATION
                                            GENERAL MOTORS EMPLOYEES
                                                 DOMESTIC GROUP TRUST
                                            THERMO ELECTRON BALANCED
                                                 INVESTMENT FUND

                                            By:  PECKS MANAGEMENT PARTNERS LTD.

                                            By: /s/ Arthur W. Berry
                                                -------------------

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